The era of highly active antiretroviral therapy (HAART) has led to a considerable decline in the HIV disease progression rates and HIV-1-related opportunistic infections especially in developed countries. Unfortunately, antiretroviral treatment for almost 90 per cent of the HIV-infected population is not available because of cost concerns. Although a number of studies have shown uniform impact of HAART on disease progression, its effect on treating HIV infection of the brain and its manifestations, such as AIDS dementia complex (ADC), remains unclear. Along with the reasons why AIDS dementia complex continues to be a problem in the era of HAART, this review also discusses the changes in ADC patterns with HAART and its relevance in developing countries such as India. In addition, an overview of various biological, molecular and therapeutic aspects that may influence HIV dementia (HIV-D) is provided.