The objective of this analysis was to systematically review the evidence for virtual reality (VR) therapy in an adult post-stroke population in both custom built virtual environments (VE) and commercially available gaming systems (CG). MEDLINE, CINAHL, EMBASE, ERIC, PSYCInfo, DARE, PEDro, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were systematically searched from the earliest available date until April 4, 2013. Controlled trials that compared VR to conventional therapy were included. Population criteria included adults (>18) post-stroke, excluding children, cerebral palsy, and other neurological disorders. Included studies were reported in English. Quality of studies was assessed with the Physiotherapy Evidence Database Scale (PEDro). Twenty-six studies met the inclusion criteria. For body function outcomes, there was a significant benefit of VR therapy compared to conventional therapy controls, G = 0.48, 95% CI = 0.27, 0.70, and no significant difference between VE and CG interventions (P = 0.38). For activity outcomes, there was a significant benefit of VR therapy, G = 0.58, 95% CI = 0.32, 0.85, and no significant difference between VE and CG interventions (P = 0.66). For participation outcomes, the overall effect size was G = 0.56, 95% CI = 0.02, 1.10. All participation outcomes came from VE studies. VR rehabilitation moderately improves outcomes compared to conventional therapy in adults post-stroke. Current CG interventions have been too few and too small to assess potential benefits of CG. Future research in this area should aim to clearly define conventional therapy, report on participation measures, consider motivational components of therapy, and investigate commercially available systems in larger RCTs. Prospero CRD42013004338.