In this article, we summarize the role of CD8⁺ T cells during natural and antiretroviral therapy (ART)‐treated HIV and SIV infections, discuss the mechanisms responsible for their suppressive activity, and review the rationale for CD8⁺ T cell‐based HIV cure strategies. Evidence suggests that CD8⁺ T cells are involved in the control of virus replication during HIV and SIV infections. During early HIV infection, the cytolytic activity of CD8⁺ T cells is responsible for control of viremia. However, it has been proposed that CD8⁺ T cells also use non‐cytolytic mechanisms to control SIV infection. More recently, CD8⁺ T cells were shown to be required to fully suppress virus production in ART‐treated SIV‐infected macaques, suggesting that CD8⁺ T cells are involved in the control of virus transcription in latently infected cells that persist under ART. A better understanding of the complex antiviral activities of CD8⁺ T cells during HIV/SIV infection will pave the way for immune interventions aimed at harnessing these functions to target the HIV reservoir.