Deregulation of mitochondrial function is a common feature in multiple aspects of aging. In addition to playing a role in aging-associated disease, decline in mitochondrial energy metabolism is likely to be important in the development of metabolic disease. Furthermore, altered mitochondrial function is a conserved feature in caloric restriction--a dietary intervention that delays aging in diverse species. The transcriptional co-activator PGC-1alpha is a critical regulator of mitochondrial energy metabolism and biogenesis. PGC-1alpha is uniquely poised as a potential target for correcting the effects of age on mitochondrial decline. We describe the cellular and tissue specific mechanisms of PGC-1alpha regulation and illustrate how these pathways may be involved in the aging process.