MDD and anxiety disorders are highly prevalent among persons who have MS and have been associated with decreased adherence to MS treatment and poorer functional status and quality of life. Effective treatment is available for MDD, but this disorder continues to be underdetected and undertreated by MS providers. Treatment with pharmacotherapy is particularly challenging in this patient population, given the somatic symptom overlap between MS and depression and the increased burden of side effects. Larger randomized, controlled trials are needed to elucidate further the effectiveness of pharmacotherapy and to identify subgroups of patients who would benefit from this type of treatment for depression. There have been few rigorous studies of the prevalence and impact of anxiety disorders, substance use disorders, or serious mental illness such as bipolar disorder or schizophrenia, in MS samples.