Sen. Ted Kennedy died shortly before midnight Tuesday at his home in Hyannis Port, Mass., at age 77.
The man known as the "liberal lion of the Senate" had fought a more than year-long battle with brain cancer, and according to his son had lived longer with the disease than his doctors expected him to.
"We've lost the irreplaceable center of our family and joyous light in our lives, but the inspiration of his faith, optimism, and perseverance will live on in our hearts forever," the Kennedy family said in a statement. "He loved this country and devoted his life to serving it."
Sen. Edward Moore Kennedy, the youngest Kennedy brother who was left to head the family's political dynasty after his brothers President John F. Kennedy and Sen. Robert F. Kennedy were assassinated.
Kennedy championed health care reform, working wages and equal rights in his storied career. In August, he was awarded the Presidential Medal of Freedom -- the nation's highest civilian honor -- by President Obama. His daughter, Kara Kennedy, accepted the award on his behalf.
Sen. Edward M. Kennedy, known as Ted or Teddy, was diagnosed with a malignant brain tumor in May 2008 and underwent a successful brain surgery soon after that. But his health continued to deteriorate, and Kennedy suffered a seizure while attending the luncheon following President Barack Obama's inauguration.
For Kennedy, the ascension of Obama was an important step toward realizing his goal of health care reform.
At the Democratic National Convention in August 2008, the Massachusetts Democrat promised, "I pledge to you that I will be there next January on the floor of the United States Senate when we begin the great test."
Sen. Kennedy made good on that pledge, but ultimately lost his battle with cancer.
Kennedy was first elected to the Senate in 1962, at the age of 30, and his tenure there would span four decades.
A hardworking, well-liked politician who became the standard-bearer of his brothers' liberal causes, his career was clouded by allegations of personal immorality and accusations that his family's clout helped him avoid the consequences of an accident that left a young woman dead.
But for the younger members of the Kennedy clan, from his own three children to those of his brothers JFK and RFK, Ted Kennedy -- once seen as the youngest and least talented in a family of glamorous overachievers -- was both a surrogate father and the center of the family.
And certainly it was Ted Kennedy who bore many of the tragedies of the family -- the violent deaths of four of his siblings, his son's battle with cancer, and the death of his nephew John F. Kennedy Jr. in a plane crash.
Edward Moore Kennedy was born in Brookline, Mass., on Feb. 22, 1932, the ninth and youngest child of Joseph P. Kennedy and Rose Fitzgerald Kennedy.
His father, a third-generation Irish-American who became a multimillionaire businessman and served for a time as a U.S. ambassador to Britain, had risen high and was determined that his sons would rise higher still.
Overshadowed by his elder siblings, Teddy, as he was known to family and friends, grew up mostly in the New York City suburb of Bronxville, N.Y., and attended private boarding schools. He was expelled from Harvard during his freshman year after he asked a friend to take an exam for him.
After a two-year stint in the Army, Kennedy returned to earn degrees at Harvard and then the University of Virginia law school. He married Virginia Joan Bennett, known by her middle name, in 1958. The couple would have three children, Kara, Teddy Jr. and Patrick.
By the time he reached adulthood, tragedy had already claimed some of his siblings: eldest brother Joe Jr. was killed in World War II, sister Kathleen died in a plane crash, and another sister, Rosemary, who was mildly retarded, had to be institutionalized following a botched lobotomy.
But then the family hit its pinnacle in 1960, when John F. Kennedy became president.
His brother's ascension created a political opportunity, and Joe Kennedy decided he should take over JFK's Senate seat. Ted Kennedy was only 28 at the time -- two years short of the required age -- so a family friend was found to hold the temporary appointment.
In 1962, Ted Kennedy -- backed by his family money and the enthusiasm his name generated among Massachusetts' Catholics, was elected to the Senate.
In 1963, President John F. Kennedy was assassinated in Dallas. His brother Robert became the focus of the family's -- and much of the country's -- dreams.
Following the tragedy in Dallas, Robert and Ted Kennedy became closer than they had ever been as children.
"When I was working for Robert Kennedy, there was hardly a day in which the two of them didn't physically get together, I would say at least three or four times," said Frank Mankiewicz, who served as an aide to Robert Kennedy. "I mean, if, if Sen. Robert Kennedy wasn't in his office, and nobody knew where he was, chances are he was seeing Ted about something."
Five years later, while pursuing the Democratic presidential nomination in 1968 against Lyndon Johnson, Sen. Bobby Kennedy was shot and killed. That left Ted as the only surviving Kennedy son.
"He seriously contemplated getting out of politics after Robert's death," said Kennedy biographer Adam Clymer. "He thought, you know, it might just be too much. He might be too obviously the next target and all of that. But he decided to stick it out and as he said on more than one occasion, pick up a fallen standard."
Kennedy was seen by many as his brothers' heir, and perhaps he could have won the White House had he stepped into the presidential race then. But he didn't. And the very next year there occurred a tragedy that would forever block Ted Kennedy's presidential ambitions.
In July 1969, following a party on Martha's Vineyard, Kennedy drove off a bridge on the tiny Massachusetts island of Chappaquiddick. The car plunged into the water. Kennedy escaped, but his passenger did not.
Kennedy later said he dived into the water repeatedly in a vain attempt to save Mary Jo Kopechne, one of the "boiler room girls" who had worked on Bobby Kennedy's campaign. But Kopechne, 28, drowned, still trapped in the car.
Questions arose about how Kennedy had known Kopechne -- he denied any "private relationship," and Kopechne's parents also insisted there was no relationship -- and why he failed to report the accident for about nine hours.
Kennedy pleaded guilty to a misdemeanor charge of leaving the scene of an accident. He received a two-month suspended sentence and lost his driver's license for a year, but the political price was higher.
Kennedy was re-elected to the Senate in 1970, but the accident at Chappaquiddick effectively squashed his presidential hopes.
He ran unsuccessfully for the Democratic nomination in 1979 against incumbent President Jimmy Carter.
Once when his daughter Kara, then 19, was passing out campaign leaflets, a man took one and said to her, "You know your father killed a young woman about your age, don't you?"
Sen. Ted Kennedy was not done confronting personal tragedy.
In 1973, 12-year-old Teddy Jr. was diagnosed with bone cancer, and he had to have a leg amputated. Kennedy's marriage to Joan deteriorated. Some blamed her drinking, others cited his alleged womanizing. The couple divorced in 1981.
In contrast, Kennedy's career in the Senate continued to flourish.
He supported teachers' unions, women's and abortion rights, and health care reform. He sponsored the Family and Medical Leave Act. And he was seen as a stalwart of the Democratic Party, delivering several rousing speeches at conventions.
Former Boston Glober reporter Tom Oliphant, who covered Kennedy's career in Washington, observed, "It's not all back slapping and, and personal relationships. I think one of the things that sets Kennedy's politics apart is his, what I call his dirty little secret. He works like a dog."
Political analyst Mark Shields said Kennedy's "concerns were national concerns, but his forum for achieving his ends and changing policy, became the Senate. And he mastered it like nobody else I've ever seen."
But another family incident exposed Kennedy's vulnerabilities and held him up to public censure.
A nephew, William Kennedy Smith, was accused of raping a woman at the family's estate in Palm Beach, Fla. The case generated lurid headlines around the world. Kennedy was at the estate at the time of the alleged attack and had been at the bar where Smith met his accuser.
Eyebrows were raised even further when a young woman who had been with Kennedy's son Patrick that night revealed that she had seen the senator roaming around the house at night, wearing an oxford shirt but no trousers.
Smith was acquitted following a highly sensational trial, but the incident definitely left a dent in Kennedy's armor. His alleged heavy drinking and womanizing were widely lampooned, and in October 1991 he thought it prudent to be low-key in his opposition to Supreme Court nominee Clarence Thomas, who had been accused of sexually harassing a former subordinate.
Kennedy's life, both professional and personal, took a turn for the better in 1992.
He married Victoria Reggie, a divorced attorney with two children from a previous marriage, Curran and Caroline. That year Kennedy also supported Bill Clinton, an open admirer of the Kennedy clan.
"Well, sometime during our courtship, I realized that I didn't want to live the rest of my life without Vicki," Kennedy said about his wife of nearly 30 years. "And since we have been together, it's made my life a lot more fulfilling. I think more serene, kind of emotional stability."
Elected in 1992, President Bill Clinton appointed Kennedy's sister, Jean Kennedy Smith, ambassador to Ireland. And in 1994, Kennedy had the satisfaction of seeing his son Patrick elected to the House of Representatives from Rhode Island.
But tragedy returned that year.
In May 1994, Jacqueline Kennedy Onassis died of cancer. Kennedy had remained close to his sister-in-law, who once quit her job at a publisher's after it came out with an unflattering biography of Ted.
Kennedy had served as a surrogate father for many of his nephews and nieces, but he may have been closest to Jackie's children, Caroline and John F. Kennedy Jr.
He was horrified when in July 1999, five years after Jackie's death, John Jr. and his bride of two years, Carolyn Bessette Kennedy, along with her sister Lauren Bessette, were killed when the small plane John was piloting crashed off the Massachusetts island of Martha's Vineyard.
Sen. Kennedy led the family during the harrowing wait for information as Coast Guard crews searched for the missing plane.
When the bodies were retrieved from the ocean, Kennedy and his two sons went to identify the remains. The senator's eulogy for his nephew who "had every gift but length of years" and "the wife who became his perfect soul mate" touched grief-stricken Americans.
It was an all-too-familiar sight for those who remember Ted Kennedy mourning the deaths of his brothers John and Robert, and helping the family bear up after the deaths of Robert's sons David and Michael.
For decades, it was Ted Kennedy who carried the burden and led the way as the patriarch of a family seen as America's answer to royalty.