Reduced oxygen (O₂) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic micro environment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O₂ level could affect their activity during muscle regeneration. In this review, we present the idea that O₂ levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms under lying myogenesis and muscle regeneration in hypoxia and depict the rapeutic strategies using changes in O₂ levels to promote muscle regeneration. Severe hypoxia (£1% O₂) appears detrimental for myogenic differentiation in vitro, whereas a 3–6%O₂ level could promotemyogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity andmyogenesis throughmechanismsdependent and independent of hypoxiainducible factor‐1a. Finally, hyperbaric oxygen therapy and transplantation of hypoxia‐conditionedmyoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patientswith severemuscle damage.—Chaillou, T. Lanner, J.T. Regulation ofmyogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity. FASEB J. 30, 3929–3941 (2016). www.fasebj.org