In response to controversy over a trial in Cambodia that was halted earlier this year, this document, written for a broad audience, addresses a range of issues regarding tests of the antiretroviral drug tenofovir in healthy uninfected individuals. The clinical trials, taking place in Africa, Asia and the Americas, aim to see whether Tenofovir can protect against HIV infection in those who are at high risk of exposure to the virus — so-called Pre-Exposure Prophylaxis, or PREP. But its use raises a whole set of concerns regarding its potential impact on trial volunteers and their communities, including the prospects for encouraging drug-resistant strains of HIV to emerge and higher risk sexual behaviour.