Although recurrent Herpes simplex virus type 1 (HSV-1) infections are quite common in humans, little is known about the exact molecular mechanisms involved in latency and reactivation of the virus from its stronghold, the trigeminal ganglion. After primary infection, HSV-1 establishes latency in sensory neurons, a state that lasts for the life of the host. Reactivation of the virus leads to recurrent disease, ranging from relatively harmless cold sores to ocular herpes. If herpes encephalitis-often a devastating disease-is also caused by reactivation or a new infection, is still a matter of debate. It is widely accepted that CD8(+) T cells as well as host cellular factors play a crucial role in maintaining latency. At least in the animal model, IFNγ and Granzyme B secretion of T cells were shown to be important for control of viral latency. Furthermore, the virus itself expresses factors that regulate its own latency-reactivation cycle. In this regard, the latency associated transcript, immediate-early proteins, and viral miRNAs seem to be the key players that control latency and reactivation on the viral side. This review focuses on HSV-1 latency in humans in the light of mechanisms learned from animal models.