Satellite cells are unipotent stem cells involved in muscle regeneration. However, the skeletal muscle microenvironment exerts a dominant influence over stem cell function. The cell intrinsic complexity of the skeletal muscle niche located within the connective tissue between fibres includes motor neurons, tendons, blood vessels, immune response mediators and interstitial cells. All these cell types modulate the trafficking of stimuli responsible of muscle fibre regeneration. In addition, several types of stem cell have been discovered in skeletal muscle tissue, mainly located in the interstitium. The majority of these stem cells appear to directly contribute to myogenic differentiation, although some are mainly implicated in paracrine effects. This review focuses on one of these classes of stem cells known as adult stem cells, which following their identification in the last decade have been used for therapeutic purposes, mainly in animal models of chronic muscle degeneration. Emerging literature identifies other myogenic progenitors generated from pluripotent stem cells as potential candidates for the treatment of skeletal muscle degeneration. However, adult stem cells still represent the gold standard for future comparative studies.