Clinical recurrence of herpes simplex virus (HSV) disease may occur when latent HSV escapes the state of latency and begins again to enter the lytic reproduction cycle. Recent investigation revealed HSV latency in peripheral sensory ganglia and an intra-axonal viral transport between the periphery and the appropriate sensory ganglia. As all previous attempts to demonstrate latent HSV in ocular structures have failed, the neuronal hypothesis for HSV latency and recurrences is the most probable. The consequences for therapy and prophylaxis of HSV disease are discussed.