Skeletal muscle regeneration and adaptation to exercise require the actions of muscle satellite cells. Muscle satellite cells are thought to play an integral role in the process of exercise adaptation, but have also been shown to possess the capacity to fully regenerate muscle tissue following destructive muscle injury. We now know that molecular regulation of satellite cells involves the coordinated actions of a series of transcriptional networks that leads to myogenic commitment, cell-cycle entry, proliferation, and terminal differentiation. Additionally, Pax7 is a paired-box transcription factor that has been identified as playing a critical role in satellite cell regulation. It remains debatable, however, whether Pax7 is required for the specification of satellite cells and (or) whether it is playing a vital role in self-renewal and maintenance of the satellite cell population. In recent years, the emergence of atypical myogenic progenitor populations has added a new dimension to muscle repair, and significant interest has been focused on identifying populations such as bone-marrow-derived stem cells that have the ability to contribute to muscle. Interestingly, elucidating the molecular regulation of myogenic progenitor populations has involved animal models of muscle regeneration, with questionable relevance for human muscle adaptation to exercise. This paper highlights the current state of knowledge on the molecular regulation of satellite cells, explores the potential contribution of atypical myogenic progenitors, and discusses the information gathered from animal regeneration models in terms of its relevance to the process of exercise adaptation.