Herpes simplex virus (HSV) is a common co-infection in persons infected with human immunodeficiency virus type 1 (HIV-1). Chronic perianal ulceration from herpes simplex virus type 2 (HSV-2) was one of the first opportunisitc infections identified among patients with AIDS. Subsequent research has established that the natural history of HSV-2 is altered in co-infected persons as they experience more frequent clinical and subclinical reactivation of HSV than persons infected only with HSV-2. In addition, there are accumulating data to suggest a significant biological interaction between these two viruses that result in more efficient sexual transmission of HIV-1 and an increased rate of HIV replication during both clinical and subclinical HSV reactivation.