Highly active antiretroviral therapy (HAART) has had a significant impact on the natural history of human immunodeficiency virus (HIV) infection, leading to a remarkable decrease in its morbidity and mortality, but is frequently associated with clinical and metabolic complications. Fat redistribution syndrome or lipodystrophy, hyperlipidaemia, insulin resistance and diabetes have been extensively reported in subjects treated with new, potent antiretroviral regimens. The potential long-term consequences of HAART-associated metabolic alterations are not completely understood, but an increased risk of premature coronary artery disease has been reported in young HIV-positive persons receiving HAART. On the other hand, the use of potent and expensive antiretroviral combinations in developing countries is very restricted and is unlikely to slow the AIDS pandemic, leading to a desperate need for a vaccine. Despite 20 years of effort, it is still a long way off, even also considerable progress has been made in understanding this problem.