Virtual reality (VR) is a developing technology that has recently attracted the attention of healthcare practitioners. Recently, VR systems have been used to treat pain symptoms. The present study aims to evaluate the VR effectiveness on chronic pain management. A systematic literature search was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Keywords were used to discover the potentially eligible studies. The primary focus of the present investigation was to evaluate the possible effect of VR-assisted treatments on chronic pain, especially in the commonly occurring low back and neck pain. Nine studies reporting randomized controlled trials were included in the present study. VR-mediated interventions demonstrated significant improvement for pain symptoms in patients experiencing chronic pain. In addition, VR-mediated therapy decreased pain intensity and disability in the case of chronic neck pain compared to control conditions. However, the VR interventions showed a statistically non-significant improvement in chronic low back pain when experimental groups were compared with controls. VR therapy positive effect on chronic pain did not differ from the one reported for other types of interventions for pain management, as physical exercise and laser therapy. Taken together, these findings showed that currently available lines of evidence on the effect of VR-mediated therapy in chronic pain management, despite pointing towards possible therapeutical benefits of the VR-based intervention, are overall inconclusive and that more research on VR-assisted therapy for chronic pain is needed.