Our objective was to review the current body of evidence supporting the efficacy of self-management programs in individuals with multiple sclerosis (MS) and other chronic neurological conditions. We reviewed published literature using standardized search terms; examined self-management interventions in a variety of chronic neurological disorders, including MS; and classified studies using the evidence classification established by the American Academy of Neurology. We reviewed 527 abstracts, of which 39 met our inclusion criteria for evaluation. Of the 39 studies, 3 provided class I evidence assessing the efficacy of self-management interventions: a randomized controlled trial of a telephone counseling program for health promotion in MS, a home-based exercise program for reducing falls in people with Parkinson disease, and the comparison of a fitness center program versus a home-based exercise program for people with traumatic brain injury. The remaining studies provided additional support for self-management interventions with a lesser degree of methodologic rigor (class II, class III, or class IV evidence). We concluded that self-management strategies are applicable to chronic neurological diseases, but a need exists for more rigorous studies in this area. We provide recommendations for future intervention study methodologies with a specific emphasis on MS care.