Lopate's longest-running program on WBAI was Round Midnight, a weekly late-night show, which featured interviews and free-form discussion on a variety of topics with listeners who called in to the station.

Lopate also appears regularly at the 92nd Street Y, where he interviews celebrities and moderates his ongoing panel series "Comparing Notes".

The show's Peabody Award-winning format typically consisted of four interviews ranging from twenty to forty minutes in length and covered a broad range of topics including current events, history, literature, the arts, including jazz and gospel music, food and wine (he has won three James Beard Awards), and science.

Lopate interviewed politicians, poets, painters, novelists, filmmakers, actors, dancers, and more than a few Nobel and Pulitzer Prize winners.

One was called "Please Explain", in which he talked with experts on a wide variety of topics that were not tied to book or movie releases and could be described as general interest.

[5] The other feature was called "Underreported", in which Lopate delved deeply into political and social issues deemed not to have received sufficient media coverage.

[8] In February 2017, a producer discussed with human resources at WNYC multiple comments Lopate had made to her that she considered sexually provocative.

The February incident led to an investigation that "resulted in one-on-one anti-harassment training for him and a warning to Lopate that he was creating an uncomfortable work environment."

"[9] On December 21, 2017, with the "MeToo" movement in full swing across the country, WNYC fired both Lopate and Jonathan Schwartz, stating that investigations found that each individual had violated WNYC's standards "for providing an inclusive, appropriate, and respectful work environment";[10] they had been placed on leave 15 days earlier pending investigations.