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Science responded to the challenge of AIDS by rapidly identifying aetiology, describing pathogenesis and transmission routes, and developing diagnostic tests and treatment. However, this did not prevent the global spread of HIV, with 25 million fatal cases so far, another 33 million infected, and disastrous socioeconomic and demographic consequences. In spite of unprecedented political attention and financial resources, the response is falling further behind the growth of the epidemic. This is partly due to the unique characteristics of the virus, such as persistent infection, vertical transmission and a variability that allows it to escape immunity and antiretroviral drugs, and partly due to human characteristics such as a strong procreative instinct, drug use and ostracism. Denial, myths and complacency are major obstacles to rational measures. With no cure or vaccine in sight, scaling up prevention is of paramount importance. To meet the goal of universal access to prevention, treatment and care by 2010 would require a quadrupling of funding to an estimated US$42 billion by 2010, including adequate overall strengthening of healthcare systems, but in any case, the world will have to learn to live with HIV for the foreseeable future.