The recording and measurement of central and peripheral nervous system responses can provide important information during the development and the application of virtual reality (VR). Although studies on electroencephalographic, evoked potentials, and peripheral psychophysiological changes in connection with VR exposure are still preliminary, they show that reliable data can be obtained even in immersive VR conditions. There is no firm evidence that neurophysiological equipment—sensors and cables—may increase subjects' discomfort and affect their ability to interact with the virtual environments, but additional study is needed to clarify this issue. Suggestions as to how to limit potential interferences are summarized here. Two main lines of research are emerging: one seeking psychophysiological correlates of reaction and adaptation to stimuli and task variables in an attempt to understand more about human-VR interaction, and the other looking for ways to use psychophysiological responses to automatically control aspects of the virtual environments or other external devices. The main results emerging from the first group of studies indicate that psychophysiological measures of brain activity—notably EEG and event-related responses—may be used to distingush between automatic and controlled modes of processing. Additionally, peripheral measures, notably skin-resistance levels, are proposed as objective correlates of presence and of the outcome of specific VR-based desensitization therapies. There is no clear-cut evidence that brain waves may index unwanted effects on the central nervous system of VR exposure, but this issue deserves further study. The results of the second line of research seem to indicate that VR-induced psychophysiological responses can be used to develop assistive devices for people with disabilities or to control hands-free interaction within any virtual environment (for example, in highly demanding conditions). A related and promising field of application is that of neurofeedback, wherein VR may play an important role in increasing the motivational/ attentional span of clients, and, ultimately, the effectiveness of treatment protocols. Given these premises, it is suggested that research on psychophysiological correlates of VR should be incremented along the lines already delineated and possibly include also groups of subjects at risk for adverse affects.