Mitochondrial biogenesis (synthesis) has been observed to occur in skeletal muscle in response to chronic use. It also occurs in cardiac muscle during growth and hypertrophy, and it may be impaired during the aging process. This review summarizes the literature on the processes of mitochondrial biogenesis at the biochemical and molecular levels, with particular reference to striated muscles. Mitochondrial biogenesis involves the expression of nuclear and mitochondrial genes and the coordination of these two genomes, the synthesis of proteins and phospholipids and their import into the organelle, and the incorporation of these lipids and proteins into their appropriate locations within the matrix, inner or outer membranes. The emphasis is on the regulation of these events, with information derived in part from other cellular systems. Although descriptions of mitochondrial content changes in heart and skeletal muscle during altered physiological states are plentiful, much work is needed at the molecular level to investigate the regulatory processes involved. A knowledge of biochemical and molecular biology techniques is essential for continued progress in the field. This is a promising area, and potential new avenues for future research are suggested.