Technological advances, lower cost, and greater availability of extended reality (XR) have led to more widespread applications and uptake of these technologies. Simulated environments can be used to study, measure, and influence human behavior in a variety of situations, and there are many examples of application in education, training, and rehabilitation, among others. However, the quality of the user experience and effectiveness of these applications are influenced by a variety of factors including the design of, and interaction with, the technology. This chapter presents an overview of human factors/ergonomics (HF/E) issues associated with XR with reference to user experience models defined in early virtual reality research. Using case examples that show how multisensory and multimodal interaction techniques can enhance the realism and efficacy of the user experience, and how XR technology can be used to deliver engaging and effective rehabilitation programs for older users, the importance of HF/E considerations are highlighted. Recommendations for future research include: the need for deeper understanding regarding optimum design of simulation content and multimodal user interaction; cost/benefit analysis taking into account user characteristics and the context of use; a provision of guidelines to aid technology producers during the design process for development of new XR applications; and standardized protocols for the evaluation of user experiences.