Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is a member of a family of transcription coactivators that plays a central role in the regulation of cellular energy metabolism. It is strongly induced by cold exposure, linking this environmental stimulus to adaptive thermogenesis. PGC-1α stimulates mitochondrial biogenesis and promotes the remodeling of muscle tissue to a fiber-type composition that is metabolically more oxidative and less glycolytic in nature, and it participates in the regulation of both carbohydrate and lipid metabolism. It is highly likely that PGC-1α is intimately involved in disorders such as obesity, diabetes, and cardiomyopathy. In particular, its regulatory function in lipid metabolism makes it an inviting target for pharmacological intervention in the treatment of obesity and Type 2 diabetes.