Stiff-man syndrome, a rare disorder characterized by intermittent spasms and stiffness of the axial muscles, is associated with an electromyographic pattern of continuous motor unit activity in affected muscles. Since the initial description in 1956, the stiff-man syndrome has been reported to occur in various clinical and neurologic settings. In this study, we reviewed the current state of knowledge about this syndrome, defined diagnostic criteria, provided a long-term follow-up of the disorder, and assessed rehabilitative attempts in affected patients. Use of rigorous criteria that identify patients who have the stiff-man syndrome is important because the initial clinical manifestations are similar to those of other neuromuscular diseases. Analysis of 13 patients with stiff-man syndrome examined at the Mayo Clinic during the past 30 years revealed that treatment with diazepam decreased the muscle spasms. Because some muscle spasms usually persist, rehabilitation is an important adjunct that may further improve function when it is centered on the treatment of low-back pain and hyperlordosis, mobility problems, gait abnormalities, and muscular stiffness.