Responding effectively to AIDS requires that program planners and implementers "know your epidemic and your response." Key to planning an effective HIV prevention response is knowing who is most affected by HIV, the extent to which HIV is prevalent among the population and different subgroups, and the risk behaviors, laws, policies, and settings that may facilitate the transmission of HIV. Key questions in planning an effective national HIV prevention response include: What is the epidemic scenario? Is it low, concentrated, generalized or hyperendemic? Where, among whom and why are new HIV infections happening? Where and how fast are infections moving? What are the legal, human rights, gender, socioeconomic and cultural drivers of epidemic? Have the most effective and feasible strategies been prioritized for the local context? Have the risks of the current strategy been analyzed? Have the human and financial resources for an effective response been assessed? Have the wider benefits of prevention programs been assessed? This short publication is a handy guide to all those working in the AIDS response, and especially those working with key populations at higher risk of exposure to HIV.