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Cellular manipulation techniques, which create in vitro disease-in-a-dish models, provide opportunities for high-throughput screening in physiologically relevant conditions against the backdrop of a species accurate genetic background. However, with the advancement of technologies such as induced pluripotent stem cells (iPSCs) the list of desired characteristics has expanded to include the ability to generate infinite amounts of multiple cell types derived from a single genetic source without repeated and ethically contentious biopsies. This technology has been applied extensively to many diseases, both inherited and communicable, and increasingly within the context of HIV, is being leveraged to uncover mechanisms of pathogenesis, target latent reservoirs, and screen for optimal drug dosages which limit adverse drug reactions. From the perspective of a geographical region disproportionately affected by HIV, these models hold even greater promise as, in parallel, we come to appreciate the extent of how Africa's extraordinary genetic diversity impacts disease progression and treatment. On this basis it would be prudent for researchers to fully harness the iPSC technology tool kit with the view towards eradicating HIV. Here, we have examined the exciting progress made towards developing relevant iPSC models within the context of three key tissues affected by HIV: 1) the cells of the immune system, 2) the neurological space, and 3) the role of the liver., (Copyright © 2022. Published by Elsevier B.V.)