Human immunodeficiency virus type 1 (HIV-1)—infected persons have high rates of herpes simplex virus type 2 (HSV-2) infection, ranging from 50% to 90% in studies of HIV-infected populations from different parts of the world. Genital herpes in persons with HIV type 1 (HIV-1) infection is associated with more-severe and chronic lesions, as well as increased rates of asymptomatic genital shedding of HSV-2. Nucleoside analogues (acyclovir, valacyclovir, and famciclovir) decrease the frequency and severity of HSV-2 recurrences and asymptomatic HSV-2 reactivation and are effective, safe, well-tolerated drugs in patients with HIV-1 infection. These anti-HSV drugs may result in additional clinical and public health benefits for persons with HIV-1 and HSV-2 coinfection by decreasing HIV-1 levels in the blood and genital tract. Given these benefits, HIV-1—infected persons should be routinely tested for HSV-2 infection using type-specific serologic tests. Persons with HSV-2 infection should be offered HSV-2 education and treatment options. Studies to quantify the potential clinical and public health benefits of treating individuals who have HIV-1 and HSV-2 coinfection with anti-HSV therapy are underway.