Many studies indicate that herpes simplex virus (HSV) seropositivity increases the risk of acquiring HIV, with fewer studies also indicating that HSV-2 infection increases the risk of transmitting HIV. In a recent meta-analysis, HSV-2 infection increased the risk of HIV-acquisition two-fold. This increased risk may occur by HSV-2 reactivation disrupting the epithelial barrier and recruiting activated CD4 cells, which are target cells for HIV infection, into the lesion. In vivo and in vitro studies assessing the effect of HSV-2 on HIV transmission demonstrate that HIV-infected CD4 cells are recruited to HSV-infected lesions and that HSV regulatory proteins (ICP0, ICP4, VP16) may upregulate HIV replication, thus increasing the frequency and titre of mucosal HIV shedding. This may occur during both clinical and asymptomatic HSV reactivation. Plausibly, antiherpetic therapy could reduce HIV transmission by decreasing HIV plasma load and/or mucosal HIV shedding, but a proof-of-concept trial is needed to demonstrate this. It also appears that individuals co-infected with HIV and HSV-2 have more frequent HSV recurrences than individuals infected with HSV-2 alone. There is a strong correlation between decreasing CD4 count and increasing rates of HSV reactivation, suggesting that reactivation is linked to immunosuppression. The IHMF recommends that individuals with HIV should be serologically tested for HSV-2. HSV-2 infection should be targeted as a modifiable risk factor for HIV acquisition by testing, counselling and preventing acquisition through behavioural interventions, treatment and antiviral suppression.