We describe the history of DUX4, starting with the FSHD genetic linkage studies of the early 1990s, and continuing through three key milestones: identification of the DUX4 gene in the D4Z4 repeat array in 1999 [24], discovery of DUX4 toxicity [25], DUX4 mRNA characterization with a PAS 3’ of D4Z4 and DUX4 protein detection in FSHD muscle cells [26]. The gene discussed is DUX4; the disease is facioscapulohumeral muscular dystrophy.