Considerable progress has been achieved in relating environmental stimuli and viral genetics to herpes simplex virus reactivation. The cytokines IL-1, IL-6, nerve growth factor NGF, and interferons have been implicated in herpes simplex virus reactivation. These molecules may act as signals which convey important information about the environment to the latent viral genome. Herpes simplex virus latency associated transcript expression is important for viral reactivation. The function of these unique viral RNA's is not completely understood, but they appear to be necessary for the efficient establishment of a latent infection in the ganglion. A better understanding of the mechanisms underlying the herpes simplex virus reactivation can be expected to lead to novel effective treatments for herpes simplex diseases.