Peroxisome proliferator-activated receptor gamma (PPARgamma) a member of the nuclear transcription factor superfamily is playing a role in colon carcinogenesis. Although not all in vivo models agree, PPARgamma seems to have suppressive effects in this process favoring apoptosis and inhibiting the cell cycle by inducing expression of apoptosis and senescence proteins. With the recent discovery that anti-diabetic class of drugs thiazolidinediones act through activation of PPARgamma, interest in this transcription factor has increased as it can now be pharmacologically activated in order to obtain tumor suppression. In addition, thiazolidinediones and other PPARgamma agonists possess PPARgamma-independent anti-tumor effects. Although PPARgamma agonists may not by themselves be capable to induce clinical tumor regression, their combination with chemotherapy drugs or other targeted therapies is worth pursuing in the treatment of colorectal carcinoma.