The herpes simplex and varicella-zoster viruses are members of the subfamily alpha herpesviruses with specific properties of the virion and with the capacity to establish latent infections in humans. The genome of each of these viruses has been determined with an estimate of the number of genes and proteins encoded. The biology and molecular events of the herpes simplex virus productive and latent infection have been detailed with the use of both in vitro and in vivo model systems. The neuron is the site of latency in the ganglia with a limited transcription of genes expressed during the latent period. The specific molecular regulation of latency and reactivation are not well established. There are co-cultivation, electron microscopy, and biochemical studies that support the concept of corneal latency, although this has not been proven conclusively. Details about the varicella-zoster virus biology and molecular events are not as well advanced since animal models have been lacking. The biology of the productive infection (varicella) is different from herpes simplex virus infection since the portal of entry is the respiratory system. Data support the concept of the maintenance of latency within satellite cells in the ganglia rather than within neurons. There are multiple genes expressed during this latency. These features may explain the different clinical presentations and course of reactivation (zoster) compared with herpes simplex virus reactivation.