Mechanisms responsible for energy management in the cell and in the whole organism require a complex network of transcription factors and cofactors. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) has emerged as a master regulator of mitochondrial biogenesis and function, thus becoming a crucial metabolic node. We present an overview of the mechanisms by which PGC-1 alpha is regulated, including the transcriptional regulation of PGC-1 alpha expression and the fine-tuning of its final activity via posttranslational modifications. Am J Clin Nutr 2011; 93 (suppl):884S-90S.