This review covers the rationale, mechanisms, and availability of commercially available virtual environment-based interventions for stroke rehabilitation. It describes interventions for motor, speech, cognitive, and sensory dysfunction. Also discussed are the important features and mechanisms that allow virtual environments to facilitate motor relearning. A common challenge is the inability to translate success in small trials to efficacy in larger populations. The heterogeneity of stroke pathophysiology has been blamed, and experts advocate for the study of multimodal approaches. Therefore, this article also introduces a framework to help define new therapy combinations that may be necessary to address stroke heterogeneity.