Regeneration of adult skeletal muscle involves the activation, proliferation and differentiation of satellite cells - quiescent tissue-specific stem cells occupying a specialised niche beneath the basal laminae of myofibres. Recent studies show that transplanted satellite cells both generate new muscle and undergo self-renewal. Data from cell culture experiments suggest that self-renewal occurs through the return to quiescence of cycling progeny. Several molecules have been implicated in the regulation of satellite cell quiescence, activation and renewal, including the transcription factors Pax7, MyoD and Myf5, the cell-surface glycoprotein CD34, and the membrane lipid sphingomyelin. Evidence suggests that non-satellite cell types from muscle interstitium and bone marrow also give rise to myonuclei, although their contributions relative to the satellite cell remain to be established.