Background Nowadays, information technologies are being widely adopted to promote healthcare and rehabilitation. Owing to their affordability and use of hand-free controllers, vision-based systems have gradually been integrated into motor rehabilitation programs and have greatly drawn the interest of healthcare practitioners and the research community. Many studies have illustrated the effectiveness of these systems in rehabilitation. However, the report and design aspects of the reported clinical trials were disregarded. Objective In this paper, we present a systematic literature review of the use of vision-based serious games and virtual reality systems in motor rehabilitation programs. We aim to propose a research methodology that engineers can use to improve the designing and reporting processes of their clinical trials. Methods We conducted a review of published studies that entail clinical experiments. Searches were performed using Web of Science and Medline (PubMed) electronic databases, and selected studies were assessed using the Downs and Black Checklist and then analyzed according to specific research questions. Results We identified 86 studies and our findings indicate that the number of studies in this field is increasing, with Korea and USA in the lead. We found that Kinect, EyeToy system, and GestureTek IREX are the most commonly used technologies in studying the effects of vision-based serious games and virtual reality systems on rehabilitation. Findings also suggest that cerebral palsy and stroke patients are the main target groups, with a particular interest on the elderly patients in this target population. The findings indicate that most of the studies focused on postural control and upper extremity exercises and used different measurements during assessment. Conclusions Although the research community's interest in this area is growing, many clinical trials lack sufficient clarity in many aspects and are not standardized. Some recommendations have been made throughout the article.