PPAR-gamma ligands constitute important insulin sensitizers that have already been approved for the treatment of human metabolic disorders. They also exert pleiotropic effects on cell proliferation and cancer and are now being explored in preclinical studies. Angiogenesis constitutes a multifaceted process that is implicated in tumor development and other benign disease states that are associated with diabetes. Recent data have further extended the crucial role of PPAR-gamma ligands as potential angiogenesis modulators, in vitro and in vivo. This review summarizes the latest knowledge of the role of PPAR-gamma ligands in angiogenesis that are related to both malignant and non-malignant disease states. Taking into careful consideration the data so far, PPAR-gamma could be considered as a therapeutic target for diverse disease states in which excessive angiogenesis is implicated, including cancer and diabetes complications.