Multiple sclerosis (MS) challenges the individual, the family, and society because (1) it can produce wide-ranging functional losses; (2) it is generally progressive with functional losses increasing over time; and (3) its course is unpredictable. Persons affected by MS respond by (1) experiencing changes in their perception of themselves and their world; (2) altering their social roles; and (3) undergoing a variety of emotional responses, especially depression and grief over the losses caused by the illness. Psychosocial interventions that address MS challenges include (1) educational interventions such as lectures, workshops, and books; (2) supportive interventions such as counseling and support groups; (3) psychoeducational interventions such as communication skills training; and (4) somatic therapies such as antidepressants. The unpredictable and progressive course of MS means that affected individuals face a lifetime of periodic challenge. Comprehensive care in MS must address the psychosocial challenges of the illness on a long-term basis. In this way MS care can address the whole patient.