The fundamental biological characteristic of herpes simplex virus (HSV) infection is its ability to establish latency and periodically reactivate, resulting in productive infectious virus. Recurrent HSV infections occur in spite of the presence of host immune responses to the virus. Because genital herpes is currently one of the three most prevalent sexually transmitted diseases worldwide, its potential public health impact has contributed to increased awareness in medical communities. The current state of knowledge on the immunological control of primary and recurrent HSV infections is reviewed, as well as the various immunebased therapeutic approaches to resultant disease. Finally, the potential benefit of immune response modifiers (IRMs), which have shown promise in early clinical studies, is discussed.