The Netherlands has approximately 20,000 registered HIV-infected patients. The current HIV prevention policy consisting of condom use and active HIV testing does not effectively mitigate the HIV epidemic in all risk groups. In July of 2012, tenofovir/emtricitabine (TDF/FTC) was approved by the American Food and Drug Administration (FDA) for pre-exposure prophylaxis (PrEP) for long-term use in persons who exhibit frequent risky and unsafe sexual behaviour. With once-daily use and good therapy compliance, TDF/FTC has proved to be effective as PrEP, and few side effects are reported. Drawbacks in the use of TDF/FTC as PrEP are the potential risk of viral resistance and reduced condom use, the relatively high cost and the intensive counselling required. In special cases, long-term PrEP could enhance the current Dutch preventive policy. Further research is needed into the practical feasibility and protective efficacy of the ad hoc use of TDF/FTC as PrEP before a high-risk contact occurs.