Satellite cells represent the primary population of stem cells resident in skeletal muscle. These adult muscle stem cells facilitate the postnatal growth, remodeling, and regeneration of skeletal muscle. Given the remarkable regenerative potential of satellite cells, there is great promise for treatment of muscle pathologies such as the muscular dystrophies with this cell population. Various protocols have been developed which allow for isolation, enrichment, and expansion of satellite cell derived muscle stem cells. However, isolated satellite cells have yet to translate into effective modalities for therapeutic intervention. Broadening our understanding of satellite cells and their niche requirements should improve our in vivo and ex vivo manipulation of these cells to expedite their use for regeneration of diseased muscle. This review explores the fates of satellite cells as determined by their molecular signatures, ontogeny, and niche dependent programming.