Over the last several years, several key advances in FSHD research, many made possible by the steady improvement in technology, have identified the molecular and genetic causes of FSHD and clarified the mechanisms of pathophysiology, leading to the discovery that FSHD is a disease of inefficient repeat-mediated epigenetic repression of the DUX4 retrogene embedded in the D4Z4 repeat units. This evidence concerns the gene DUX4 and facioscapulohumeral muscular dystrophy.