Issues relevant to the nervous system garnered substantial attention at the 18th Conference on Retroviruses and Opportunistic Infections. Several topics emerged as areas of importance both for informing current understanding of HIV-related neurologic disorders and their treatment, and for spurring future investigations. Measurable biomarkers of HIV-associated neurocognitive disorder (HAND) were a major theme, with studies ranging from new investigations of known laboratory and imaging markers to identification of novel molecules that might be investigated as potential means to follow disease activity as well as to better understand etiology of disease. Studies of pathogenesis of HAND and simian immunodeficiency virus-mediated neurologic injury added to prior understanding of lentivirus neuropathogenesis. Another broad area of investigation was the interplay between treatment with antiretroviral or adjunctive therapies and biomarkers of HAND. New data were presented on the potential importance of acute and early infection on the integrity of the central nervous system, complemented by studies of the effects of early treatment interventions.