Virus latency is a long-term pathogenic condition in patients infected with human immunodeficiency virus type-1 (HIV-1). Low but sustained virus replication in these cells is activated by stimulation with pro-inflammatory cytokines and other inducible host factors.  How these and other host factors re-activate latently infected cells to induce productive virus replication has remained unclear. This article summarizes critical pathways that mediate reactivation of virus replication and describes possible mechanisms of action in the re-activation of HIV-1 infection.