But the senator also navigated a rocky, painful and some say cursed, road as part of the Kennedy clan. The family has confronted monumental challenges -- including assassinations, deadly plane and car accidents, public failings, family difficulties, legislative hurdles, and most recently Ted Kennedy's devastating, terminal illness.
Through those rough waters, Ted Kennedy continued to sail on.
"The phrase that he's used with me over the years is 'Keep on keeping on,'" Boston Globe columnist Thomas Oliphant said in an interview with ABC News. "You can't puzzle through something as enormous and almost unspeakable as these tragedies are. But you can get up tomorrow and do something."
Kennedy's long battle with brain cancer was the last struggle of many during his 77 years, but the senator learned about death early on.
Born Feb. 22, 1932, as the youngest of eight, Kennedy was just 12 years old when his oldest brother, Joseph, Jr., a navy flier in World War II, was shot down during a secret bombing run in 1944. Nearly four years later in 1948, his second-oldest sister, Kathleen, died in a plane crash during a trip to the South of France at the age of 28.
Kennedy faced ups and downs as a young adult before beginning a career in politics. After graduating from Milton Academy, Kennedy enrolled at Harvard University in 1950, but was expelled for having another student take his Spanish final exam.
He then enlisted for two years in the U.S. Army, and worked at the Supreme Headquarters Allied Powers in Paris before returning to Harvard in 1956 to obtain his degree.
Kennedy then enrolled in law school at the University of Virginia, receiving his law degree in 1959. He married his first wife, Virginia Joan Bennett in 1958, with whom he had three children, Kara Anne, Edward M., Jr., and Patrick Joseph. While still in law school, Kennedy began to build his political credentials by managing his brother John F. Kennedy's 1958 Senate re-election campaign. In 1960, he served as Western states coordinator for his brother's successful democratic presidential campaign.
After his brother's victory in 1960, Kennedy went on to take a dollar-a-year job as assistant to the Suffolk County, Mass., district attorney. He won his brother's former seat in the Senate in 1962, at just 30 years old.
Tragedy struck a year later, in 1963, when his second-oldest brother, President John F. Kennedy, was assassinated.
A year later, as he was running for re-election to a full-Senate term, Ted Kennedy broke his back in the June 1964 plane crash that killed his aide, Edward Moss. The injury incapacitated him throughout the campaign. Despite his injury, he won the election with 74.4 percent of the vote.
Four years later, in 1968, his third-oldest and only surviving brother, N.Y. Sen. Robert Kennedy, was assassinated while campaigning for the presidency.
Ted Kennedy went into a period of withdrawal, resisting efforts to draft him for the 1968 presidential democratic nomination.
Kennedy Haunted By Chappaquiddick
When Ted Kennedy emerged, he came back strong, passing legislation to end quotas on immigrants and becoming a vocal critic of the Vietnam War. He was elected as the Senate majority whip in January 1969.
Yet his victory was short-lived. Six months after becoming majority whip, Kennedy was involved in a near-fatal car accident that almost ended his political career.
Following a party, Kennedy, then 37, accidentally drove his car off a narrow bridge on Chappaquiddick Island, drowning his passenger, 28-year-old Mary Jo Kopechne. Kopechne had worked on Robert's presidential campaign with a group of women known as the "boiler girls." Kennedy managed to escaped, and said he dove into the water repeatedly to rescue Kopechne, but was not able to save her. Kennedy did not report the accident for nearly nine hours.
A week later, Kennedy reported to a courthouse in Edgartown, Mass., with his pregnant wife, Joan. He was charged with a misdemeanor for leaving the scene of an accident. He pleaded guilty, and was given a two-month suspended sentence.
After a week of silence, Kennedy delivered a speech broadcast live, in which he called his failure to report the accident immediately "indefensible."
"I would understand full well why some might think it right for me to resign. This would be a difficult decision to make….And so I ask you tonight, the people of Massachusetts, to think this through with me," Kennedy said on July 25, 1969.
The Massachusetts public indeed forgave Kennedy. But unanswered questions surrounding the accident left the national public less forgiving.
In 1973, Kennedy's oldest son, Ted, Jr., was diagnosed with bone cancer and had to have a leg amputated.
On Nov. 7, 1979, Kennedy announced his decision to run for president. Although he began ahead of a weak incumbent President Jimmy Carter in the polls, a late start and a lack of a strong message hampered his campaign.
Nine months later, in August 1980, Kennedy lost the democratic nomination to Carter.
The next year, he and his wife Joan divorced. After the divorce, and before he remarried 11 years later, there were stories of womanizing and heavy drinking -- and a scandalous incident in Palm Beach, Florida in 1991.
Ted Kennedy Testifies in Nephew's Rape Trial
Kennedy went drinking on Good Friday with his son, Patrick, and nephew, William Kennedy Smith. Smith left them with a woman who later accused him of rape.
Smith was acquitted, but only after a trial that put Kennedy on the witness stand and called his own conduct into question. He addressed the issue several weeks later, in a speech at Harvard.
"I am painfully aware that the criticism directed at me in recent months involves far more than disagreements with my positions," Kennedy said on Oct. 25, 1991. "To them I say, I recognize my own shortcomings – the faults in the conduct of my public life. I realize that I alone am responsible for them, and I am the one who must confront them."
A woman, Victoria Reggie -- or Vicki, as she would later be known -- was in the audience at that Harvard speech. Reggie and Kennedy married the following year, in 1992. Reggie was interested in politics, and they both shared Catholic faith. Reggie brought two children to the Kennedy family from a previous marriage, Caroline and Curran Raclin.
Faced with enormous personal hurdles, Kennedy plowed forward.
"The issue always is what you do the next day," Oliphant said. "And more than anything else, I think that defines how he has persevered through tragedies that are almost unimaginable for, for anybody else."
Others say Kennedy lived his life similar to the way he played football.
"He'd get knocked down, he'd always get up and never stop. He'd keep coming, keep coming," said John Chester Culver, a former democratic House representative and senator for Iowa, who also played Harvard football with Kennedy. "But he never quit and he never stopped. And again, I think that is just an extraordinary quality. And it speaks to really his basic character and determination to serve."