Beginning in May 2005, the podcast explores rational thought, skeptical ideas, and famous myths from around the world and throughout history.

It has featured interviews with James Randi, and scientists, such as authors and astronomers Phil Plait and Neil deGrasse Tyson, Greg Graffin from Bad Religion, Adam Savage from the MythBusters, songwriter Jill Sobule, author Ann Druyan and science communicator Bill Nye.

At the time, Colanduno was working at a national Sports Radio network and a privately owned Alternative Rock Station (KEDG) during the overnight shift.

[3] Skepticality gained notability on September 7, 2005 during a keynote address, when Apple CEO Steve Jobs mentioned it as one of the top nine podcasts at the iTunes Music Store.

In an interview with Derek during the June 1, 2006 episode[18] of Slacker Astronomy, the naming of Asteroids 106545 Colanduno[19] and 106537 McCarthy[20] was announced to the world.