The application of molecular biology in the study of the pathogenesis of herpes simplex virus type 1 (HSV-1) has led to significant advances in our understanding of mechanisms that regulate virus behavior in sensory neurons and epithelial tissue. Such study has provided insight into the relationship of host and viral factors that regulate latency, reactivation, and recurrent disease. This review attempts to distill decades of information involving human, animal, and cell culture studies of HSV-1 with the goal of correlating molecular events with the clinical and laboratory behavior of the virus during latency, reactivation, and recurrent disease. The purpose of such an attempt is to acquaint the clinician/scientist with the current thinking in the field, and to provide key references upon which current opinions rest.