- 1941 – Rosemary Kennedy, a younger sister of President Kennedy, was believed to be mentally retarded. However, some sources have claimed she was suffering from mental illness, such as depression. Because of her increasingly violent and severe mood swings, her father, Joseph Kennedy Sr., arranged in secret for her to undergo a lobotomy. The surgery impaired her cognitive abilities even more, and as a result, she remained institutionalized until her death in 2005.
- August 12, 1944 – Joseph Kennedy Jr., the older brother of the later President Kennedy, is killed in action in a mid-air aircraft explosion over eastern England while flying a hazardous mission during World War II.
- May 13, 1948 – Kathleen Cavendish. a younger sister of the later President Kennedy, is killed in a plane crash in France along with her ill-fated companion, Peter Wentworth-Fitzwilliam.
- August 23, 1956 – Jacqueline Kennedy, the wife of then future President Kennedy, gives birth to her stillborn daughter, Arabella Kennedy. (Although the daughter was unnamed and is buried at Arlington National Cemetary next to her parents with a marker reading "Daughter", later reports indicated that the Kennedys had intended to name her Arabella.)
- August 9, 1963 – Patrick Kennedy, son of President Kennedy and First Lady Jacqueline Kennedy, born six weeks premature, dies two days after his birth.
- November 22, 1963 – U.S. President John F. Kennedy by Lee Harvey Oswald, in Dallas, Texas.
- June 19, 1964 – U.S. Senator Edward "Ted" Kennedy, the youngest brother of the late President Kennedy, is involved in a plane crash in which one of his aides and the pilot were killed. He was pulled from the wreckage by fellow senator Birch Bayh II (D-Ind.) and spent weeks in a hospital recovering from a broken back, a punctured lung, broken ribs, and internal bleeding.
- June 6, 1968 – U.S. Senator Robert F. Kennedy, a younger brother of the late President Kennedy, is assassinated by Sirhan Sirhan in Los Angeles immediately following his victory in the California Democratic presidential primary.
- July 18, 1969 – In the Chappaquiddick Incident, a car driven by Ted Kennedy goes off a bridge on Martha's Vineyard, eventually drowning his passenger Mary Jo Kopechne. In his July 25 televised statement, Kennedy stated that on the night of the incident he wondered "whether some awful curse did actually hang over all the Kennedys."
- August 13, 1973 – Joseph Kennedy II, the eldest son of Robert F. Kennedy, is the driver in a car accident that leaves one passenger, Pam Kelley, permanently paralyzed.
- November 17, 1973 – Edward Kennedy Jr., a son of Ted Kennedy, loses a portion of his right leg due to bone cancer at the age of 12.
- April 25, 1984 – David Kennedy, son of Robert F. Kennedy, dies from a Demerol and cocaine overdose in a Palm Beach, Florida hotel room.
- 1991 - William Smith, a nephew of JFK, is tried for rape, and is acquitted of all charges.
- December 31, 1997 – Michael Kennedy, son of Robert F. Kennedy, is killed in a skiing accident in Aspen, Colorado.
- July 16, 1999 – John F. Kennedy Jr., the oldest and only surviving son of JFK, is killed in a plane crash along with his wife and sister-in-law when the Piper Saratoga light aircraft he was piloting crashed into the Atlantic Ocean off the coast of Martha's Vineyard due to pilot error.
