Herpes simplex virus (HSV)-2 is a lifelong infection that causes recurrent genital ulcers and, rarely, disseminated and visceral disease. HSV-1 infection is an increasingly important cause of genital ulcers. HSV infections are the most common cause of genital ulcers in adults, but acquisition and chronic infection are more commonly asymptomatic than symptomatic. Both the symptomatic and asymptomatic forms of HSV are of clinical consequence for several reasons. HSV-2 infection enhances HIV-1 acquisition and transmission. In addition, sexual and perinatal transmission can occur during asymptomatic viral shedding. Perinatal transmission is of particular concern because neonatal HSV infection results in severe morbidity to the newborn. Antiviral medicines are effective for limiting recurrence duration and decreasing transmission likelihood, although no available intervention completely prevents transmission. This fact highlights the importance of laboratory diagnostics for this lifelong infection, and the need for an HSV vaccine.