Systemic therapy is a widely used psychotherapy approach. Yet there exist few systematic reviews on its efficacy. A meta-content analysis was performed to analyze the efficacy of systemic therapy for the treatment of mental disorders in adulthood. All randomized (or matched) controlled trials (RCT) evaluating systemic/systems oriented therapy in various settings (family, couple, individual, group, multifamily group therapy) with adult index patients suffering from mental disorders were identified by database searches and cross-references in other reviews. Inclusion criteria were: index patient diagnosed with a DSM or ICD listed mental disorder, trial published in any language up to the end of 2008. The RCTs were content analyzed according to their research methodology, interventions applied, and results. Thirty-eight trials published in English, German, Spanish, and Chinese were identified, 34 of them showing systemic therapy to be efficacious for the treatment of mood disorders, eating disorders, substance use disorders, mental and social factors related to medical conditions and physical disorders, and schizophrenia. Systemic therapy may also be efficacious for anxiety disorders. Results were stable across follow-up periods of up to 5 years. There is a sound evidence-base for the efficacy of systemic therapy for adult index patients with mental disorders in at least five diagnostic groups.