Even after 25 years of experience, HIV prevention programming remains largely deficient. We identify four areas that managers of national HIV prevention programmes should reassess and hence refocus their efforts-improvement of targeting, selection, and delivery of prevention interventions, and optimisation of funding. Although each area is not wholly independent from one another, and because each country and epidemic context will require a different balance of time and funding allocation in each area, we present the current state of each dimension in the global HIV prevention arena and propose practical ways to remedy present deficiencies. Insufficient data for intervention effectiveness and country-specific epidemiology has meant that programme managers have operated, and continue to operate, in a fog of uncertainty. Although priority must be given to the improvement of prevention methods and the capacity for the generation and use of evidence to improve programme planning and implementation, uncertainty will remain. In the meantime, however, we argue that prevention programming can be made much more effective by use of information that is readily available.