Oxygen plays an important role in regulating cell differentiation in a variety of cell types. Satellite cells, which are the primary stem cells in adult skeletal muscle, are wedged between the plasma membrane of the myofiber and the basement membrane, and they contribute to muscle growth, maintenance, repair, and regeneration. Several lines of evidence suggest that satellite cells can adapt to changes in O₂ availability via molecular signaling mechanisms that convert this information into appropriate physiological responses. Understanding how cells adapt to altered physiological conditions will provide a valuable insight into the underlying mechanisms that regulate cellular homeostasis. Here we will summarize the current knowledge about the molecular mechanisms responsible for myogenic differentiation under hypoxia. We will focus especially on how hypoxia inhibits myogenic differentiation.