Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of a class of nuclear hormone receptors intimately involved in the regulation of expression of myriad genes that regulate energy metabolism, cell differentiation, apoptosis and inflammation. Although originally discovered as a pivotal regulator of adipocyte differentiation, the roles that this transcription factor play in physiology and pathophysiology continue to grow as researchers discover its influence in the function of many cell types. This review highlights the roles that PPARgamma play in the regulation of gene expression associated with normal cell physiology as well as the pathophysiology of multiple diseases including obesity, diabetes and cancer. Additionally, naturally occurring and pharmaceutical ligands for the receptor as well as the potential role of PPARgamma as the receptor responsible for fatty acid-induced effects on gene expression will be described.