While great strides have been made in the treatment of HIV infection with highly active antiretroviral therapy, an actual cure remains out of grasp. One confounding factor is the persistence of a small population of infected cells containing transcriptionally silent but reactivatable HIV proviruses. Following cessation of highly active antiretroviral therapy, these latently-infected cells serve as an inoculum for re-establishing an active infection. Recent progress in our understanding of the molecular mechanisms underlying HIV proviral latency will be reviewed. Recent advances in the study of transcriptional regulation and the completion of the Human Genome Project underscore the role of chromatin and the site of viral integration on HIV transcription. Finally, experimental therapies designed to eliminate the latent population will be highlighted.