Dysregulation in the gamma motoneuron circuitry is proposed as one mechanism to explain the development of trigger point activity in myofascial pain syndrome. Dysregulation in this context is defined operationally as significantly (and functionally) different levels of electrical activity detected in the same muscle on the left and right sides of the body that is persistently present with movement of that muscle. Neurophysiological concepts as they pertain to muscles and motor control principles are reviewed. Research is integrated that ties together material from diverse fields of psychology and medicine. Dysregulation in the gamma motoneuron circuitry may lead to disinhibition of muscle that causes it to remain hyperactive after contraction, generate excessive electrical activity during movement, and/or inappropriately coactivate with other muscles during movement. Any or all of these phenomena may occur with dysregulation. Such dysregulation may be corrected by learning. Immediate clinical implications are discussed, including the addition of specifically targeted neuromuscular retraining procedures via surface electromyography, as well as some conceptual and research issues that require further clarification.