Significant synergistic interactions have been observed between HIV and herpes simplex virus (HSV). HIV-induced immune compromise can cause frequent and persistent HSV disease, while poorly controlled HSV replication may influence HIV pathogenicity and transmission. HSV-2 seroprevalence is high in HIV-infected cohorts worldwide, with rates of over 80% for HSV-1 and ranging from 33% to more than 80% for HSV-2. As seen in HIV-negative individuals, HSV-2 coinfection is associated with female gender, older age and black ethnicity. HSV infection is commonly under-diagnosed in HIV-infected individuals, although the use of PCR for HSV detection in mucocutaneous swabs and HSV type-specific serology can improve the diagnostic yield. In HIV-1-infected patients with frequent clinical episodes of HSV reactivation, suppressive antiviral therapy may prove beneficial in controlling HSV disease while also reducing HSV-mediated promotion of HIV replication. Antiretroviral therapy leads to a gradual recovery of HSV-specific T-cell responses and a reduction in HSV-related morbidity, indicating that successful management of coinfection should target both HIV and HSV replication. The aim of this review is to address the more speculative issues surrounding the management of HSV/HIV coinfection and to summarize the data that inform them.