Since 1978, the study of health and behavior has become a major focus of scientists in psychology, psychiatry, nursing, neuroscience, and in traditional medical science disciplines. Investigation of psychological or behavioral influences on biological systems has established that biobehavioral processes such as stress play an important role in disease processes. An excellent example of the interactions between stress and health outcomes is the reactivation of latent herpes simplex virus (HSV) leading to recurrent lesions. This article describes what is currently known about HSV latency and reactivation and considers some mechanisms by which stress-induced changes in the host's immune and nervous systems might allow for either the establishment or reactivation of latent viral infections.