HAART treatment has greatly improved life expectancy of HIV-1-infected individuals. Unfortunately, latency still remains the major barrier towards HIV-1 eradication. Efforts to identify viral and host cell proteins involved in latency remain important research areas to win this war against HIV-1. Here, we review the contributions of several factors in the establishment of latently infected cells. In addition, we also raise the possibility that RNA helicases, while playing important roles at almost every step of the HIV-1 replication cycle, could be implicated in the processes governing the establishment of these latent reservoirs.