The 25th anniversary of the first reports of a catastrophic illness later classified as AIDS and the 10th anniversary of highly active antiretroviral therapy (HAART) both occurred in 2006. Where available, HAART has revolutionised the treatment of HIV. This success has brought challenges--the unknown long-term history of treated HIV infection, the development of toxicity and drug resistance, and the ageing HIV-infected patient. Despite these advances, the number of HIV cases continues to rise in vulnerable populations in under-resourced areas of the world. These anniversaries allow us to appreciate the milestones achieved thus far and those yet to be achieved. Only a collaborative global effort will stop the epidemic from overwhelming efforts to contain it.