Several findings published within the past year have further established key roles for chromatin-modifying enzymes in the control of muscle gene expression, and have thus refined our thinking of how chromatin structure influences muscle differentiation, hypertrophy and fiber type determination. We discuss the interface between chromatin-modifying enzymes and myogenic transcription factors, signaling mechanisms that impinge on these transcriptional complexes, and how these multicomponent regulatory cascades may be exploited in the development of novel therapeutics to more effectively treat myopathies in humans.