Skeletal muscle possesses a resident, multipotent stem cell population that is essential for its repair and maintenance throughout life. Here I highlight the role of this stem cell population in muscle repair and regeneration and review the genetic control of the process; the mechanistic steps of activation, migration, recognition, adhesion, and fusion of these cells; and discuss the novel recognition of the membrane signaling that coordinates myogenic cell-cell fusion, as well as the identification of a two-part fusogen system that facilitates it.