The aim of this systematic review was to evaluate the effect of immersive and non-immersive interactive virtual reality on pain perception in patients with a clinical pain condition. Methods: The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane library and Web of Science. Two reviewers screened reports and extracted the data. A third reviewer acted as an arbiter. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and uncontrolled trials. Crossover and parallel-group designs were included. Risk of bias was assessed for all included studies. Results: Thirteen clinical studies were included. The majority of studies investigated a sample of participants with chronic pain. Six were controlled trials and seven uncontrolled studies. Controlled research showed that interactive virtual reality reduces pain associated with ankylosing spondylitis and post-mastectomy, but results are inconsistent for patients with neck pain. Findings from uncontrolled studies showed that interactive virtual reality reduced neuropathic limb pain, and phantom limb pain, but had no effect on non-specific chronic back pain. Conclusions: There is not enough evidence upon which to judge the effectiveness of the use of virtual reality for the management of pain.