Neurocognitive impairment is common in people living with HIV and AIDS. Prior to highly active antiretroviral therapy (HAART), cognitive impairment primarily affected patients with advanced disease, and was a more rapidly progressive illness. With the use of HAART, cognitive impairment improved, along with the overall health of HIV-positive patients. However, it is still a prevalent problem, even in patients with desirable CD4+ count and undetectable plasma viral load. In this review, we address the nature of HIV-related neurocognitive impairment in the HAART era, including its etiology, pathology, appropriate diagnostic tools for clinical practice and research, and rational treatment approaches.