Thiazolidinediones induce adipocyte differentiation and thereby limit proliferative potential; hence, early investigations focused on their ability to modulate cellular proliferation and apoptosis. Several lines of evidence indicate significant thiazolidinedione-mediated antitumor activity. An emerging view is that some antitumor effects are totally or partially peroxisome proliferator-activated receptor-gamma (PPARgamma) dependent, whereas others are PPARgamma independent. The aim of this review is to examine the current evidence about the molecular mechanisms by which thiazolidinediones augment cellular differentiation, inhibit cellular proliferation, and induce apoptosis. We first address the role of thiazolidinediones and/or PPARgamma on Wnt/beta-catenin signaling pathway as it affects cellular differentiation and then discuss other pathways that are also involved in differentiation as well as proliferation and apoptosis.