Obama called Kennedy the 'greatest United States senator of our time' who had picked up the torch of his fallen brothers.

The youngest Kennedy brother, also known as 'Teddy', was one of the longest serving US senators, spending 46 years in the chamber, where he was known as a liberal lion.

He followed his brothers in running for president after John F. Kennedy was gunned down while in office in 1963 and Robert Kennedy was also fatally shot in 1968 while campaigning for the presidency.

Edward Kennedy's aspirations for the White House, however, were hurt by a 1969 car accident in which he drove off a bridge and his female passenger was killed. He ran for the office once, in 1980, losing in the Democratic Party primaries to the eventual president, Jimmy Carter.

He had an illustrious career in the Senate, however, playing major roles in passing legislation on health care, civil rights and education.

He was diagnosed with brain cancer in May 2008 after suffering a seizure and underwent surgery to remove part of his brain tumour the following month. He then underwent radiation and chemotherapy treatments and made few public appearances.

'We've lost the irreplaceable centre of our family and joyous light in our lives, but the inspiration of his faith, optimism and perseverance will live on in our hearts forever,' the family statement said.

'We thank everyone who gave him care and support over this last year, and everyone who stood with him for so many years in his tireless march for progress toward justice.'