Stiff person syndrome (SPS) is a rare disease of the nervous system. Progressively severe muscle stiffness typically develops in the spine and lower extremities; often beginning very subtly during a period of emotional stress. Most patients experience painful episodic muscle spasms that are triggered by sudden stimuli. An autoimmune component is typical and patients often have other autoimmune disorders. Symptoms usually begin in the mid forties. Although it is not possible to determine the exact prevalence, it may occur in fewer that 1 per million. The disease is more common in women (the ratio is 2 women for every man affected). There is no predilection for any race or ethnic group. There is an association with diabetes and perhaps over half of patients with SPS have or will develop diabetes. Other autoimmune diseases have been found in association with SPS, for example: thyroid disease and vitiligo. There is an increased incidence of epilepsy. An important but especially rare variant of SPS is associated with breast or lung cancer. Although SPS is a serious potentially life-threatening disease, and some of the treatments have serious potential side effects; the course of SPS is variable. There are patients who, with proper treatment, are able to return to activities they enjoy.