Piskor has been fascinated by comics throughout his childhood. He was a great fan of mainstream comics such as Spider-Man, but his interest in the alternative comics developed rapidly when, at the age of 9, he saw a documentary that had Harvey Pekar reading one of his American Splendor stories.
His first major comics Deviant Funnies and the autobiographical Isolation Chamber are generally marked with dark humour. In 2003 he started his collaboration with Jay Lynch, and shortly after that with Harvey Pekar. Piskor's first major with Pekar task was illustrating stories of American Splendor: Our Movie Year, which ellaborates Pekar's experience after the release of the movie American Splendor. Piskor also illustrated Pekar's latest graphic novel Macedonia, which was released on June 26, 2007 through Villard Books.
Piskor's latest series, Wizzywig deals with Kevin "Boingthump" Phenicle, a young prodigy who becomes fascinated with social engineering, phone phreaking, and eventually computer hacking. As the series progresses, Kevin grows as well as his trials and tribulations with hacking. His endeavors make him legendary; his abilities are feared and also revered by many.
The character from the series, Kevin, is a composite of many well known phreaks and hackers such as Kevin Mitnick, Kevin Poulsen, Joy Bubbles, and many others. Volume 1: Phreak is available through Piskor's website
Piskor's drawing has been influenced by 60s and 70s underground comix scene, and he also points Robert Crumb as a major influence, but comic critics have praised Piskor for developing his own artistic style.