It has been known for more than 4 decades that exercise causes increases in skeletal muscle mitochondrial enzyme content and activity (i.e., mitochondrial biogenesis). Increasing evidence now suggests that exercise can induce mitochondrial biogenesis in a wide range of tissues not normally associated with the metabolic demands of exercise. Perturbations in mitochondrial content and (or) function have been linked to a wide variety of diseases, in multiple tissues, and exercise may serve as a potent approach by which to prevent and (or) treat these pathologies. In this context, the purpose of this review is to highlight the effects of exercise, and the underlying mechanisms therein, on the induction of mitochondrial biogenesis in skeletal muscle, adipose tissue, liver, brain, and kidney.