A broad spectrum of neuropathologic changes are encountered in the brains of heroin abusers. The main findings are due to infections, either due to bacterial spread from bacterial endocarditis, mycoses, or from HIV-1 infection. Other complications include hypoxic-ischemic changes with cerebral edema, ischemic neuronal damage and neuronal loss, which are assumed to occur under conditions of prolonged heroin-induced respiratory depression, stroke due to, for example, thromboembolism, vasculitis, septic emboli, hypotension, and positional vascular compression. Myelopathy is believed to be the result of an isolated vascular accident within the spinal cord due to an as yet unknown mechanism. A distinct entity, spongiform leukoencephalopathy, has been described mainly after inhalation of pre-heated heroin. A lipophilic toxin-induced process was considered to be due to contaminants and to be induced or enhanced by cerebral hypoxia, but a definite toxin could not be identified. At the cellular level, abnormalities in signal transduction systems and changes of various receptor densities have been reported. The exact etiology of the different neuropathological alterations associated with heroin abuse is still unclear, but may also be related to additional substances used as adulterants.