Thirty years ago the HIV-1 virus (causing AIDS) was isolated and characterized. Studies of molecular phylogeny have revealed that HIV evolved from the simian immunodeficiency virus SIVcpz during cross-species transmission events taking evidently place during hunting and during butchering of monkey meat in the timeframe 1902–1921. Kinshasa (Congo DR) is considered the epicentre of the global HIV epidemic, from where the two oldest HIVcontaining tissue samples, originating from 1959 and 1960, were found. The virus then spread from Africa to Haiti before spreading to the USA and elsewhere. The pathogenetic mechanisms of HIV-1 are complex loss of CD4+ cells, resulting in disturbances of the whole immune system, both in the cellular and humoral arms. Chronic immune activation caused by HIV is a key factor contributing to immunodeficiency. The isolation of HIV and the understanding of its life cycle enabled to launch drug development. The first drug was licenced in 1987 (NRTI class), but a single drug regimen was not sufficiently efficient. In 1995 new drugs (PI class) were invented and combination theraphy with several drugs was introduced. This led to the 10-fold reduction in AIDS and mortality in Europe. Currently available drugs are classified into 5 classes based on their mode of action, which has changed the earlier deadly disease into a well-controlled chronic infection. Despite all efforts made in the field there is currently no effective vaccine against HIV-1 available but relevant research is in progress.