Skeletal muscle formation and growth require the fusion of myoblasts to form multinucleated myofibers or myotubes. Studies of the calcium activated transcription factor NFATC2 demonstrate that cell fusion during myogenesis occurs in two distinctly regulated phases. NFATC2 controls myoblast fusion after the initial formation of a myotube and is necessary for further cell growth. Recently we have shown that following myotube formation, myotubes recruit myoblast fusion by secretion of IL-4 and prostaglandin F2alpha. Molecules that control muscle cell fusion are of great interest from a therapeutic standpoint to enhance growth of muscle after injury or to alleviate the loss of muscle mass found in disease or aging.