PGC-1 was originally identified as a transcriptional coactivator of the nuclear receptor PPARγ. The expression pattern and induction by exposure to cold have implicated PGC-1 in the regulation of energy metabolism and adaptive thermogenesis. Remarkably, PGC-1 overexpression can induce mitochondrial biogenesis and functions. Recent studies show that PGC-1 regulates the activity of several nuclear receptors and other transcription factors, and thus acts in a broader context than previously anticipated. Furthermore, PGC-1 displays the striking ability to interact with components of the splicing machinery. PGC-1 could therefore allow coordinated regulation of transcription and splicing in response to signals relaying metabolic needs. These novel findings are discussed in the context of the proposed physiological functions of PGC-1.