SummaryThe main obstacle to HIV eradication is the establishment of a long‐term persistent HIV reservoir. Although several therapeutic approaches have been developed to reduce and eventually eliminate the HIV reservoir, only a few have achieved promising results. A better knowledge of the mechanisms involved in the establishment and maintenance of HIV reservoir is of utmost relevance for the design of new therapeutic strategies aimed at purging it with the ultimate goal of achieving HIV eradication or alternatively a functional cure. In this regard, it is also important to take a close look into the cellular HIV reservoirs other than resting memory CD4 T‐cells with key roles in reservoir maintenance that have been recently described. Unraveling the special characteristics of these HIV cellular compartments could aid us in designing new therapeutic strategies to deplete the latent HIV reservoir.