The aims of this systematic review were to analyze and to compare the efficacy of the multidisciplinary treatment (MT) applied to patients with fibromyalgia and chronic fatigue syndrome (CFS). Also, predictors, mediators and moderators of results were examined. An exhaustive literature search was carried out in the databases Medline, PsycInfo, Scopus and Cochrane Library in the period 1990-2018. In total, 31 articles on fibromyalgia and six on CFS were identified. The results showed that in fibromyalgia, MT was more effective than waiting list controls (WLC) and the usual treatment, producing the most consistent improvements in functionality, pain, quality of life and physical fitness. As to CFS, there were fewer benefits than in fibromyalgia, and the MT was only more effective than the WLC, and it mainly decreased the disability. However, the evidence was not enough to confirm the superiority of MT over other active treatments, nor to consolidate the prognostic value of the predictors, mediators, and moderators of the reported results.