Addictions to licit and illicit drugs are chronic relapsing brain disorders that affect circuits that regulate reward, motivation, memory, and decision-making. Drug-induced pathological changes in these brain regions are associated with characteristic enduring behaviors that continue despite adverse biopsychosocial consequences. Repeated exposure to these substances leads to egocentric behaviors that focus on obtaining the drug by any means and on taking the drug under adverse psychosocial and medical conditions. Addiction also includes craving for the substances and, in some cases, involvement in risky behaviors that can cause death. These patterns of behaviors are associated with specific cognitive disturbances and neuroimaging evidence for brain dysfunctions in a diverse population of drug addicts. Postmortem studies have also revealed significant biochemical and/or structural abnormalities in some addicted individuals. The present review provides a summary of the evidence that has accumulated over the past few years to implicate brain dysfunctions in the varied manifestations of drug addiction. We thus review data on cerebrovascular alterations, brain structural abnormalities, and postmortem studies of patients who abuse cannabis, cocaine, amphetamines, heroin, and “bath salts”. We also discuss potential molecular, biochemical, and cellular bases for the varied clinical presentations of these patients. Elucidation of the biological bases of addiction will help to develop better therapeutic approaches to these patient populations.