BackgroundVirtual reality (VR) therapy has been explored as a novel therapeutic approach for numerous health applications, in which three-dimensional virtual environments can be explored in real time. Studies have found positive outcomes for patients using VR for clinical conditions such as anxiety disorders, addictions, phobias, posttraumatic stress disorder, eating disorders, stroke rehabilitation, and for pain management.ObjectiveThis work aims to highlight key issues in the implementation of clinical research for VR technologies.MethodsA discussion paper was developed from a narrative review of recent clinical research in the field, and the researchers’ own experiences in conducting VR clinical research with chronic pain patients.ResultsSome of the key issues in implementing clinical VR research include theoretical immaturity, a lack of technical standards, the problems of separating effects of media versus medium, practical in vivo issues, and costs.ConclusionsOver the last decade, some significant successes have been claimed for the use of VR. Nevertheless, the implementation of clinical VR research outside of the laboratory presents substantial clinical challenges. It is argued that careful attention to addressing these issues in research design and pilot studies are needed in order to make clinical VR research more rigorous and improve the clinical significance of findings.