The prevalence of herpes simplex virus type 2 (HSV-2) infection is not uniform, with some populations bearing a greater burden of disease than others. Potential risk factors that influence HSV-2 transmission rates have been identified, largely from observational prospective and retrospective studies. Risk factors can be categorized as biological or behavioural. These risk factors can be markers of population subgroups that are likely to have acquired, or are at high risk of acquiring, HSV-2. Major factors associated with HSV-2 seropositivity include female gender, race (black), history of sexually transmitted infections, increasing numbers of sexual partners, sexual contact with commercial sex workers and low socio-economic status or level of education. Age-related risk factors are important, likely reflecting the cumulative number of sex partners, age of initiation of sexual activity, and duration of sexual activity as well as chronic nature of HSV-2 infection. Understanding and identifying these factors may help to direct interventions to reduce HSV-2 transmission and acquisition. An important contributing factor to the spread of genital herpes is unrecognized virus shedding, often allowing transmission from individuals who are not aware that they are infected or who are not having a recurrence. Antiviral therapy reduces both the frequency and amount of HSV reactivation, whereas behavioural risk factors can be addressed in part with educational initiatives. Clinical history is a poor predictor of HSV-2 infection and type-specific serological testing is recommended to detect HSV-2 seropositivity.