This review synthesized the literature examining the effects of virtual reality (VR)-based exercise on physiological, psychological, and rehabilitative outcomes in various populations. A systematic review. 246 articles were retrieved using key words, such as "VR", "exercise intervention", "physiological", "psychology", and "rehabilitation" through nine databases including Academic Search Premier and PubMed. 15 articles which met the following criteria were included in the review: (1) peer-reviewed; (2) published in English; (3) randomized controlled trials (RCTs), controlled trials or causal-comparative design; (4) interventions using VR devices; and (5) examined effects on physiological, psychological, and/or rehabilitative outcomes. Descriptive and thematic analyses were used. Of the 12 articles examining physiological outcomes, eight showed a positive effect on physical fitness, muscle strength, balance, and extremity function. Only four articles examined the effects on psychological outcomes, three showed positive effects such that VR exercise could ease fatigue, tension, and depression and induce calmness and enhance quality of life. Nine articles investigated the effects of VR-based exercise on rehabilitative outcomes with physiological and/or psychological outcomes, and six observed significant positive changes. In detail, patients who suffered from chronic stroke, hemodialysis, spinal-cord injury, cerebral palsy in early ages, and cognitive decline usually saw better improvements using VR-based exercise. The findings suggest that VR exercise has the potential to exert a positive impact on individual's physiological, psychological, and rehabilitative outcomes compared with traditional exercise. However, the quality, quantity, and sample size of existing studies are far from ideal. Therefore, more rigorous studies are needed to confirm the observed positive effects.