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