Despain has worked as a graphic designer, 3D modeler, photo retoucher, and illustrator.
In October 1999, Despain left his career in video games to pursue his own projects, working and writing full-time at his home studio.
[citation needed] Besides painting for galleries and private collectors, he occasionally does professional illustration work.
His art appears on the covers of the poetry collections HUM and The Big Book of Exit Strategies by Detroit writer Jamaal May, as well as multiple young-adult fiction book covers, including "Arthur and the Minimoys" by French film mogul Luc Besson and "The Clockwork Three" by Matthew J. Kirby.
[citation needed] His Dungeons & Dragons work includes the 3.5 edition Monster Manual and Lost Empires of Faerûn.