The integration of viral cDNA into the host genome is an essential step in the HIV‐1‐life cycle and is mediated by the virally encoded enzyme, integrase (IN). Inhibition of this process provides an attractive strategy for antiviral drug design. The discovery of β‐diketo acid inhibitors played a major role in validating IN as a legitimate antiretroviral drug target. Over a decade of research, a plethora of IN inhibitors have been discovered and some showed antiviral activity consistent with their effect on IN. To date, at least two compounds have been tested in human but none are close to the FDA approval. In this review, we provide a comprehensive report of all small‐molecule IN inhibitors discovered during the years 2003 and 2004. Compilation of such data will prove beneficial in developing QSAR, virtual screening, pharmacophore hypothesis generation, and validation. © 2006 Wiley Periodicals, Inc. Med Res Rev