Human immunodeficiency virus (HIV-1) latency is clinically highlighting via the persistence of a residual viral load in cART-treated patients due to the reactivation of cellular reservoirs. Two forms of latency coexist but the contribution of the pre-integrationnal latency clearly plays a minor role in viral persistence. In contrast, the post-integrationnal latency significantly contributes to the evasion of the immune system by the HIV-1 cellular reservoir and consequently to HIV-1 pathogenesis. Although post-transcriptional mechanisms can contribute to the maintenance of viral latency, HIV-1 transcriptional inhibition is critical for the establishment and maintenance of post-integrational latency. This inhibition is a multifactorial phenomenon, making the development of anti-latency therapeutic strategies complex. These different notions will be described throughout this review.