Despite the benefits of current antiretroviral treatments, the neurological complications of HIV infection remain an important and unmet medical and social need. Drug abusers, particularly injection drug users, represent a significant group of HIV-infected patients. These individuals, whose adherence to antiretroviral therapy is generally poor, often present with a more dramatic progression to AIDS and neuroAIDS. Opiates can accelerate HIV neuropathology by acting on immune and neural cells; however, the mechanisms involved are unclear. Characterization of these mechanisms will yield new insights for the development of neuroprotective therapies in HIV patients.