HIV-associated neurocognitive disorders (HAND) are the most common preventable and treatable cause of dementia. While the incidence of the most severe form of HAND, HIV-associated dementia, has decreased since the introduction of combination antiretroviral therapy (cART), the prevalence of less severe forms of HAND has continued to rise. HAND leads to a subcortical dementia consisting of a triad of cognitive, behavior, and motor dysfunction. No single laboratory test can establish HAND, but ancillary studies including neuropsychological testing, neuroimaging studies, and cerebrospinal fluid (CSF) analysis are useful for supporting or refuting the diagnosis. More recent evidence has suggested that higher central nervous system-penetrating cART may lead to greater suppression of CSF HIV viral loads and improved cognition. Because viral control generally has been successful without eliminating cognitive dysfunction, further clinical studies that assess adjunctive neuroprotective drugs are likely to be required.