The effects of cocaine abuse on brain structure and function are numerous. Some of these effects, such as catastrophic cerebrovascular incidents, are clearly neuropathological. Others, such as persistent perfusion deficits and changes in cerebral glucose utilization, await further functional definition. More recent findings of increases in dopamine transporter density and gene induction may be neuropathologic, but could represent neuroadaptive responses to cocaine's acute actions of cocaine, manifestations of the reinforcing properties of cocaine or epiphenomena of addiction. Recent technical advances directed at bridging the gap between preclinical and clinical studies hold significant promise for advancing our understanding regarding the neuropathology of cocaine abuse and addiction.