Several advances have led to improvements in the care and prognosis of HIV+ individuals. The first is an understanding of the direct relationship between HIV replication and subsequent immunological and clinical progression, reinforcing the need to completely suppress HIV replication to control disease progression. The second is the wider availability of HAART which can provide effective suppression of HIV. The third major change is the ability to monitor HAART through the reliable and widespread measurement of plasma HIV RNA levels, which has become a routine part of clinical care. Since the introduction of highly active antiretroviral therapy (HAART) in the 1990s, there have been significant declines in the incidence rates of opportunistic infections in developed countries. HAART has clearly improved survival for individuals with HIV/AIDS, and has reduced the incidence of HIV-associated dementia (HIV-D) by 40-50% (Brodt et al., 2002). The prevalence of sensory neuropathies in advanced HIV/AIDS now exceeds 20% (Schifitto et al., 2002), and may rise further with prolonged exposure to neurotoxic HAART. HIV-D and HIV-related sensory neuropathies (HIV-SN) have a combined prevalence of about 30-50% in advanced HIV disease, suggesting that HAART does not provide complete protection against neurological damage (Bouwman et al., 1998). HIV-associated dementia (HIV-D) remains a common cause of dementia worldwide, and with HIV-related sensory neuropathies (HIV-SN) represents the commonest neurological disorders associated with AIDS. Furthermore, the temporal progression of HIV-D appears to have been altered by HAART, with most patients now showing an attenuated form of dementia, which with treatment is slowly progressive or static (Dougherty et al., 2002). This overview will review some of the outstanding questions relating to HIV-dementia, including: (a) are there differing phenotypes or temporal patterns of progression in HIV-dementia? (b) what determines these temporal patterns? and (c), what has been the impact of therapy on HIV dementia?