Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor with a key role in adipocyte differentiation. Since 1997, studies of rare mutations and common polymorphisms of the PPARgamma gene have enabled us to expand our knowledge of the role of this transcription factor in humans. Rare monogenic mutations in PPARgamma have a limited impact on the health of the population due to their low frequency but are associated with severe phenotypes such as severe insulin resistance, partial lipodystrophy, type 2 diabetes and hypertension. Conversely, common polymorphisms of PPARgamma with a relatively high frequency can have a significant impact on the general population. Although they may modulate the risk of developing type 2 diabetes, obesity and cardiovascular diseases, the data remains controversial. This review details and discusses results obtained for PPARgamma variants, whose effects sometimes appear discordant.