This time around, Brennan's defense of targeted killing by drones is likely to provide additional fodder for critics, although barring new revelations, he appears likely to be confirmed.
Deprived of the CIA post four years ago, Brennan, 57, became instead one of Obama's closest advisors on counterterrorism and homeland security. That proximity has made him a more powerful figure in the administration than the director of national intelligence - who will become his boss if he is confirmed.
Brennan, who grew up in New Jersey, is described by those who know him as a "straight arrow" and man of high morals.
"The word for John is 'intense'," said A.B. "Buzzy" Krongard, a former top CIA official who was once Brennan's boss there. "John's all about commitment."
His long working hours at the CIA and the White House are legendary. Obama, in announcing Brennan's nomination on Monday, quipped: "I'm not sure he's slept in four years."
Brennan pledged, if confirmed, to "make it my mission to ensure that the CIA has the tools it needs to keep our nation safe and that its work always reflects the liberties, the freedoms, and the values that we hold so dear."
Brennan was at the president's side during some of the most significant security incidents during his first term.