The peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors, initially described as molecular targets for compounds which induce peroxisomal proliferation. PPAR-gamma, the best characterized of the PPARs, is a ligand-activated transcription factor and a key regulator of adipogenic differentiation and glucose homeostasis. PPAR-gamma ligands have recently been demonstrated to affect proliferation, differentiation and apoptosis of different cell types. Recent in vitro and in vivo studies suggest the importance of specific PPAR-gamma ligands as cell-cycle modulators, establishing their antineoplastic properties. In this review, the latest knowledge on the role of PPAR-gamma ligands as cell-cycle modulators is presented, discussing also their role in cell proliferation, apoptosis and cancer.