For the past 64 years, a member of the famous Kennedy clan has been in either the White House, Senate, or House of Representatives, a lineage which is likely to be broken.
Kennedy, who at 42 has struggled with substance abuse and mental health issues for years, announced last week that he will be devoting his life to advocacy on behalf of the mentally and emotionally disabled.
Among the many who issued statements about the startling announcement was the Rhode Island bishop who feuded with Kennedy last fall over abortion.
"I am sure that the congressman's decision was a difficult one to make given his very long and strong commitment to public service," said Bishop Thomas Tobin. "I wish him well and pray that God will bless all his future endeavors."
A son of former congressman Joseph P Kennedy II is now seen as the most likely family member to enter the political arena in the foreseeable future.
Joseph P Kennedy III, a 29-year-old Harvard Law School graduate, former Peace Corps volunteer and currently an assistant district attorney in Barnstable County, Mass., has made numerous appearances at Democratic party events and has expressed some interest in seeking political office.
His twin brother, Matthew, works in the Obama administration and has indicated a preference for a career in business rather than politics.
Joe Kennedy III, whose father heads Citizens Energy, may have his sights on the seat currently held by Democratic Congressman Bill Delahunt, who, according to reports, is viewed as being vulnerable by the GOP and has not yet announced whether he will seek re-election to the House of Representatives this fall.