Purpose of ReviewThe purpose of this review is to provide an overview of central nervous system (CNS) infections in patients living with HIV (PLWH) and to highlight their diverse etiologies, clinical presentations, and diagnostic approaches.Recent FindingsKey innovations in the field include new treatments for cryptococcal meningitis and tuberculous meningitis. Characterization of the clinical manifestations of neurosyphilis and prevention strategies in high-risk populations such as PLWH will be highlighted.SummaryCNS infections are an important cause of morbidity and mortality in PLWH, especially in patients with severe immunosuppression. These opportunistic infections present a particular challenge because of their life-threatening nature, difficulty in diagnosis, and gaps in knowledge regarding treatment. Tuberculosis, cryptococcal meningitis, toxoplasmosis, neurosyphilis, CMV, JC virus, and herpes viruses are among the most common CNS infections. Early detection, prompt diagnosis, and initiation of appropriate therapy in conjunction with antiretroviral treatment remain critical to improve outcomes and enhance quality of life. A comprehensive understanding of these infections is essential for healthcare providers to optimize care and reduce the burden of CNS-related complications in people with HIV/AIDS.