The human tragedy and mounting crisis of orphans and vulnerable children demands a global response. Attention now is required to generate the resources and to expand the partnerships needed to respond adequately, and with common objectives, over the long term. This framework reflects a broad international consensus around goals, principles, strategies and programming that should guide such a response. It is directed particularly to senior government officials as well as organizational leaders and decision-makers who have the capacity to mobilize and sustain a significant increase in the global response. The application of this framework will add momentum and solidarity to international, regional, national and local efforts to confront HIV/AIDS and mitigate its impact on children.