HIV-1 latency is considered the last hurdle toward viral eradication in the presence of antiretroviral therapy. Studies of viral latency in vivo are complicated by the low frequency of latently infected cells found in HIV-1 patients. To be able to study the signaling pathways and viral determinants of latency and reactivation, we have developed a novel method that generates high numbers of latently HIV-1 infected cells, which are derived from human primary CD4⁺ T lymphocytes. This method allows for the study of different aspects of HIV-1 latency, such as the transcription factors needed for viral reactivation and the signaling pathways involved. In this review, we describe in detail an experimental protocol for the generation of HIV-1 latency using human primary CD4⁺ T cells. We also present the salient points of other latency models in the field, along with key findings arising from each model.