The neurotropic herpes viruses, HSV-1, HSV-2 and VZV, colonize and establish latent infection in human peripheral sensory ganglia. Recurrent diseases due to reactivation of these viral pathogens can take place despite an effective immune response. Molecular, cellular, physiological and immune mechanisms work in concert to enable the establishment of latency, the maintenance of the latent state for the entire life of the host, and the reactivation infection. Although all three viruses belong to the same family and establish latent infection in the same tissue, the clinical pattern of their reactivation is quite different. This review covers current knowledge of the basis of these infections, and offers a theory explaining the basis of HSV-1 latent infection and the differences of the disorders caused by HSV-1 and VZV reactivation in humans.