: Given the challenges of life-long adherence to suppressive HIV antiretroviral therapy (ART) and possibilities of comorbidities, such as HIV association neurocognitive disorder, HIV remission and eradication are desirable goals for people living with HIV. In some individuals, there is evidence that HIV persists and replicates in the CNS, impacting the success of HIV remission interventions. This article addresses the role of HIV CNS latency on HIV eradication, examines the effects of early ART, latency-modifying agents, antibody-based and T-cell enhancing therapies on the CNS as well as ART interruption in remission studies. We propose the integration of CNS monitoring into such studies in order to clarify the short-term and long-term neurological safety of experimental agents and treatment interruption, and to better characterize their effects on HIV CNS persistence.