To systematically evaluate existing evidence from published systematic reviews of clinical trials for the effectiveness of rehabilitation for improving function and participation in persons with multiple sclerosis (MS).A literature search was conducted using medical and health science electronic databases (MEDLINE, EMBASE, CINAHL, PubMed, Cochrane Library) up to January 31, 2016.Two reviewers independently applied inclusion criteria to select potential systematic reviews assessing the effectiveness of organized rehabilitation for persons with MS. Data were summarized for type of interventions, type of study designs included, outcome domains, method of data synthesis, and findings.Data were extracted by 2 reviewers independently for methodological quality using the Assessment of Multiple Systematic Reviews. Quality of evidence was critically appraised with the Grades of Recommendation, Assessment, Development, and Evaluation.Thirty-nine systematic reviews (one with 2 reports) evaluated best evidence to date. There is "strong" evidence for physical therapy for improved activity and participation, and for exercise-based educational programs for the reduction of patient-reported fatigue. There is "moderate" evidence for multidisciplinary rehabilitation for longer-term gains at the levels of activity (disability) and participation, for cognitive-behavior therapy for the treatment of depression, and for information-provision interventions for improved patient knowledge. There is "limited" evidence for better patient outcomes using psychological and symptom management programs (fatigue, spasticity). For other rehabilitation interventions, the evidence is inconclusive because of limited methodologically robust studies.Despite the range of rehabilitative treatments available for MS, there is a lack of high-quality evidence for many modalities. Further research is needed for effective rehabilitation approaches with appropriate study design, outcome measurement, type and intensity of modalities, and cost-effectiveness of these interventions.