Peroxisome proliferator-activated receptor-gamma (PPARgamma), one of three ligand-activated transcription factors named PPAR, has been identified as a molecular target for cancer chemopreventive agents. PPARgamma was initially understood as a regulator of adipocyte differentiation and glucose homeostasis while later on, it became evident that it is also involved in cell differentiation, apoptosis, and angiogenesis, biological processes which are deregulated in cancer. It is now established that PPARgamma ligands can induce cell differentiation and yield early antineoplastic effects in several tumor types. Moreover, several bioactive natural products with cancer protecting potential are shown to operate through activation of PPARgamma. Overall, PPARgamma appears to be a prevalent target ally to cancer chemopreventive agents and therefore pursuing research in this area is of great relevance.