A myofascial trigger point (TrP) is a point of focal tenderness, associated with a taut band of muscle fibers, that can develop in any skeletal muscle. TrPs are a common source of pain and motor dysfunction in humans and other vertebrates. There is no universally accepted pathophysiology to explain the etiology, symptomatology and treatment of TrPs. This article reviews and extends the author's previously published hypothesis for the pathophysiology of TrPs, "Trigger Points and Central Modulation-A New Hypothesis." The author proposes that central nervous system-maintained global changes in α-motoneuron function, resulting from sustained plateau depolarization, rather than a local dysfunction of the motor endplate, underlie the pathogenesis of TrPs.