Sen. John McCain, R-Arizona, said he planned to examine Brennan's record closely.
"I appreciate John Brennan's long record of service to our nation," McCain said in a statement, "but I have many questions and concerns about his nomination to be director of the Central Intelligence Agency, especially what role he played in the so-called enhanced interrogation programs while serving at the CIA during the last administration, as well as his public defense of those programs."
Even as she praised his record, Sen. Dianne Feinstein, D-California, said she planned to raise the CIA detention and interrogation issue with Brennan.
The fact that Brennan is coming from the West Wing and has frequently talked about the president's views on camera could make him political fodder, said Frances Fragos Townsend, CNN's national security contributor.
"He's got to expect that (Capitol) Hill is going to treat him as a political person who is fair game now, rightly or wrongly," she said.
On Monday, Brennan said he was prepared to work with lawmakers on both sides of the aisle and field their questions.
"While the intelligence profession oftentimes demands secrecy," he said, "it is critically important that there be a full and open discourse on intelligence matters with the appropriate elected representatives of the American people."