[5] The show is composed primarily of interviews with prominent figures in various fields, among them entertainment and the arts, culture, journalism, and global current affairs.

The program also features commentary and interviews from a range of regular contributors, including Maureen Corrigan, David Bianculli, Dave Davies, Ken Tucker, Kevin Whitehead, John Powers, Lloyd Schwartz, Geoffrey Nunberg, Justin Chang, and Nick Quah.

[10] David Edelstein was let go from his position as film critic for the show on November 27, 2018, for comments made in the wake of Bernardo Bertolucci's death.

The program is produced and edited by Amy Salit, Phyllis Myers, Ann Marie Baldonado, Sam Briger, Lauren Krenzel, Heidi Saman, Therese Madden, Seth Kelley, Thea Chaloner, and Susan Nyakundi.

[14] When pressing news requires, the show has gone live, such as during the Soviet coup attempt of 1991, and in the aftermath of the Boston Marathon bombing on April 19, 2013.

The show's theme song, a jazz piece called "Fresh Air", was composed for the program by Joel Forrester of The Microscopic Septet.

[19] In 1993, NPR, Fresh Air, and Gross were presented with the George Foster Peabody Award with praise for her "probing questions, revelatory interviews, and unusual insights".

Her patient, persistent questioning in thousands of interviews over four decades has pushed public figures to reveal personal motivations behind extraordinary lives—revealing simple truths that affirm our common humanity.