The peroxisome proliferator-activated receptor gamma (PPAR gamma) has recently been implicated in the pathogenesis of inflammatory bowel disease (IBD) and colon cancer. The observation that PPAR gamma agonists, through immune modulation, protect against inflammatory processes in the intestine justified their expedient evaluation in the clinical management of IBD. PPAR gamma agonists are reported to have both tumor-promoting and -inhibiting effects in models of colon cancer. These differences can, in part, be explained by PPAR gamma-independent effects of PPAR gamma agonists and by differences in the models used. Because it is still unclear how PPAR gamma impacts on colon cancer, careful monitoring of patients receiving PPAR gamma agonists and additional basic research is indicated before recommendations on the use of PPAR gamma ligands in colon cancer can be made.