A recent study has provided important clues towards the identity of the host genes that conspire to promote post-integration latency of human immunodeficiency virus (HIV). Various genes controlling transcription, histone deacetylation and proteasome-mediated protein degradation have emerged as potential players. If the desired, but difficult, goal of complete virus eradication in HIV-infected patients is ever to be realized, the latent reservoir of HIV proviruses must be cleared. Understanding the molecular basis for viral latency is the key first step.