Combination therapy, comprising at least three anti-human immunodeficiency virus (anti-HIV) drugs, has become the standard treatment of AIDS. Since 1996, highly active antiretroviral therapy (HAART) was designed to rapidly control HIV replication. It has had a significant impact on patient health and progression of AIDS in developed countries but its success has not been complete. HAART strategy still suffers from issues of patient compliance, cost, deleterious side effects and emerging drug resistance. Therefore it is logical to look for agents that inhibit different viral targets. In addition to the fusion, reverse transcription and protein formation processes, the HIV replicative cycle offers various other events that can be considered as potential targets for chemotherapeutic intervention. Amongst them integration is a key step and integrase (IN), one of the three viral enzymes, has been rapidly identified as a rational target for many years. To date, four molecules have entered in clinical trials. The present article reviews the increasing number of patents on small molecule HIV-1 integrase inhibitors in the 1998-2005 period, from the pioneer ones (discovery of selective strand transfer inhibitors) to the last patents including the actual molecules under clinical trials.