The paper examines the situation of HIV/AIDS globally, and in Africa. Up to recently higher education institutions had done very little in terms of response to the pandemic. The Kelly report (Kelly 2001) as well as reports from workshops sponsored by the Association of Commonwealth Universities (ACU) and the South African Vice Chancellors' Association (SAUVCA) indicate the serious impact of the pandemic in terms of the fiscal situation, and in terms of the negative social impacts on university communities. At the same time the reports indicate some good examples of what has been done by individuals or groups within the Universities "with a fire in their belly". The examples cover a range of areas including what has been done in teaching, research, as well as among communities of which the institutions are a part. The central message of the paper is that higher education institutions must develop a comprehensive HIV prevention programme which runs through and drives each of the following: HIV/AIDS policy and strategy development; Developing culturally appropriate prevention messages; Tackling socio-economic factors; Establishing partnerships; Sustaining awareness and education; Challenging denial and stigma; Situating prevention in a community context; Linking care to prevention; Rigorous scientific reflection.