Patients with multiple sclerosis (MS) may experience progressive problems of many kinds, often over decades. Ambulation, muscle strength and coordination, bladder function, vision, behavior, and cognition may eventually be affected. The diagnosis is based on clinical features and laboratory studies, but no definitive test exists. The rate of misdiagnosis may be as high as 30%. Treatment consists of pharmacotherapy for symptoms, therapy for the disease itself, and experimental therapies. Long-term management of MS can be a worthwhile challenge for primary care physicians. Helpful resources include neurologists with an interest in the disease, regional treatment and rehabilitation centers, and local MS societies.