NPR personalities Noah Adams, Alex Cohen and Mike Pesca often served as substitute hosts for the program.

The Savage Nation - substitute host for Michael Savage on several occasions, most recently the October 24, 2011 show.

Scott Van Pelt (substitute host, 2006-present)

Noelle McCarthy, Wayne Mowat, Paul Brennan, and Chris Whitta are substitute hosts.

Kevin Ebi was substitute host during the campaign; Ross resumed his place as host following his unsuccessful campaign run.

The thinking seems be that should Mr. Letterman progress rapidly, as he seems to be doing, it will not be necessary to go to any substitute hosts.

Mark Jones (substitute host, 2007-present)

Jeff Thisted and Shandi Finnessey served as substitute hosts.

John Saunders (substitute host)

Mr. O'Reilly's ratings fell over the four weeks from 2.1 million viewers, to 1.9 million, but five of those shows had substitute hosts.