Rosemary Kennedy, another sister, spent her adult life in an institution because of mental retardation and the effects of a failed lobotomy.
In more recent years, assorted Kennedy cousins also have met tragedy.
There was Michael Kennedy, one of Bobby's sons, who died in a skiing accident in Colorado, when he hit a tree while tossing a football on the slopes. He was 39. David Kennedy, another of Robert's children, died of a drug overdose in Palm Beach, Fla, in 1984. He was 28.
Ted Kennedy is no stranger to tragedy or scandal. In 1964 he survived a small plane crash that killed two people. Kennedy suffered multiple spinal fractures that led to a lifelong struggle with back pain.
In 1969, he drove a car off a bridge on Chappaquiddick Island in Massachusetts after a party. Mary Jo Kopechne, an aide riding with him, died. Controversy over the case helped to snuff Kennedy's presidential dreams.
While some have never forgiven Kennedy for the episode, his service in the Senate has made him one of the most influential lawmakers of his time. Many of those he has helped said they are heartbroken by the cancer diagnosis.
Brian Hart of Bedford, Mass., got to know Kennedy after his soldier son John Hart was killed in an ambush in Iraq in 2003.
Kennedy attended the funeral at Arlington National Cemetery and listened for a half hour as Brian Hart explained that his son had felt unsafe riding in Humvees that lacked protective armor.
Kennedy subsequently held hearings and pushed through legislation guaranteeing that all Humvees would be armored and that all soldiers would have body armor.
"Sen. Kennedy single-handedly has saved hundreds of lives. We feel he never received the credit for the work he did on this," Hart said. "Honestly, my wife and I are very sad, heartbroken in fact, when we heard the news today."
Lilly Ledbetter, 70, of Jacksonville, Ala., met Kennedy this year, after he sponsored the Lilly Ledbetter Fair Pay Act. The measure would correct a Supreme Court decision that gutted wage discrimination protections for women workers. Ledbetter was the original plaintiff in the case.