The proliferator-activated receptor gamma co-activator 1/estrogen-related receptor (PGC-1/ERR) transcriptional axis is involved in the control of mitochondrial biogenesis. The PGC-1/ERR pathway plays a dual role in cancer, depending on the specific cellular or tissue context and the environmental stimuli. The PGC-1/ERR axis has been shown to be essential for functional cancer cell motility and metastasis, leading to malignant transformation in breast and melanoma cancer progression. This pathway has also been shown to suppress prostate cancer progression and metastasis. The expression of PGC-1α is characterized by high expression levels in tissues, including kidney, skeletal muscle, liver, heart, neural tissue, and blood mononuclear cells, which exhibit greater energy demand caused by increased mitochondrial activity.57–59 The vast number of different tissues or physiological contexts in which PGC-1α is expressed reflects the large number of different NRs and TFs that are regulated by PGC-1α, possibly including all three estrogen-related receptors (ERRα, ERRβ, and ERRγ), SRC-1, and glucocorticoid receptors (GR), as well as the tumor suppressor p53, PPARγ, forkhead box protein O1 (FoxO1), hepatocyte nuclear factor 4α (HNF-4α), nuclear respiratory factor 1 (NRF-1), the cAMP response element binding protein (CREB), and the signal transducer and activator of transcription 6 (STAT-6).