He won his first Senate seat in 1972, when he was just 29 years old.
But that early victory, came tragedy. Shortly after he was elected, his first wife and infant daughter were killed in a car crash. His two sons were badly injured.
"I felt like a piece of me had died," Biden said.
Biden took the oath of office at his sons' bedsides. And in order to care for them, began his Capitol Hill career commuting from Wilmington to Washington. It's a practice he's never stopped.
A powerful voice in Washington, Biden is the chairman of the Foreign Relations Committee. He voted to authorize the war in Iraq, but has since become an outspoken critic.
No stranger to presidential campaigns, Biden sought the top spot himself for the first time in 1987, but was forced to pull out following allegations of plagiarism.
"There will be other campaigns and I'll be there," he said.
He had his share of medical problems, too: surgery to repair two aneurysms.
"I joke and say those two craniotomies I had for these … aneurysms, they took the top of my head off," he said.
Outspoken and candid - he's sometimes a little too candid.
"You cannot go to a 7-11 or a Dunkin' Donuts unless you have a slight Indian accent," he said recently.
Biden is a man who's been know to say what he thinks. But he's learning.
At the April 2007 MSNBC debate, moderator Brian Williams asked: "Sen. Biden, words have, in the past, gotten you in trouble. Words that were borrowed and words that some found hateful. Can you reassure voters in this country that you would have the discipline you would need on the world stage, Senator?"
"Yes," Biden said, curtly.