John and Jacqueline Kennedy had their first child, Caroline, in 1957; John Jr. was born two weeks after his father won the presidency. A third child, Patrick, died two days after his birth in August 1963. After a long succession of elderly presidents, it was refreshing for many to see the Kennedy family's youth and vitality. One image in particular stood out: that of John Jr. playing under the president's desk in the Oval Office. When JFK died, it was another image that would prove indelible: Jacqueline Kennedy whispering to John Jr. to be sure to give a military salute as the casket carrying the president passed by.

The president's extended family was large, wealthy, and powerful. President Kennedy named his brother Robert attorney general so, as he put it, his brother could “get some legal experience" before getting a job.” Congress was not amused by the joke, and although Robert served ably, it later passed a law forbidding the president to make appointments of close relatives to federal office. President Lyndon Johnson, seeing Robert as a rival, maneuvered to keep him off the Democratic ticket in 1964 by stating that no cabinet secretary would be considered. Robert responded wryly that he was sorry to take so many capable officeholders down with him.

In the November 1962 mid-term elections, John Kennedy's younger brother Edward (Teddy) successfully ran for the Senate seat JFK had vacated in Massachusetts. After the president's death, Robert Kennedy was elected as a senator from New York state and became a frontrunner for the Democratic presidential nomination in 1968. This second Kennedy run for the White House was cut short by another assassin's bullet. After winning the California Democratic primary that June, Robert Kennedy was gunned down by Sirhan Sirhan. Edward Kennedy would also make a run for the Oval Office in 1980 when he unsuccessfully challenged President Jimmy Carter's renomination. Despite his defeat, Edward Kennedy remained an active and senior member of the US Senate until his death in 2009.