This publication provides guidance to governments, international organizations, nongovernmental organizations (NGOs) and other members of civil society in monitoring and evaluating (M&E) HIV prevention programmes for most-at-risk populations. It is designed primarily for programme managers and others involved in planning and implementing M&E of programmes and projects for most-at-risk populations at both national and subnational levels. This framework includes methods and tools that can be applied at the national, and perhaps more appropriately, at the subnational level. Unlike interventions aimed at the general population, interventions for most-at-risk populations are often implemented on a subnational basis, as most-at-risk populations are not uniformly spread across a country. Rather, they are often concentrated in large cities, border areas, and towns with large migrant or tourist populations. Because interventions for most-at-risk populations are often planned and implemented at the local level, M&E efforts should also occur at the local as well as the national level.