Addiction to drugs and alcohol is often undiagnosed and untreated. Physicians are often unaware or have negative attitudes regarding these patients, such as the perception that treatment is ineffective. Addiction--psychological dependence with or without tolerance and withdrawal--is essentially compulsive uncontrolled substance use despite physical, psychological, or social consequences. We now have an understanding of the 2 major neurological pathways involved in addiction. First, the mesolimbic dopamine reward pathway, which is essential for survival, can be physically altered by drug abuse to result in uncontrolled cravings. Second, the decision-making prefrontal cortex, which suppresses inappropriate reward response, can also be altered by drug abuse. Thus, accelerated "go" signals and impaired "stop" signals result in uncontrolled use despite severe consequences. Further, addicts can be predisposed to addiction by genetic defects in reward pathway neurotransmission and stress-related developmental brain abnormalities. Relapse to drug use can occur because of stress or cue-related reward pathway stimulation or even by a single drug dose. Individualized treatment of addiction, including pharmacological and cognitive-behavioral interventions, can be as successful as treatment of other chronic diseases. Several pharmaceuticals are available or under study for these disorders. Waiting for the addict to "be ready" for treatment can be dangerous and detoxification alone is often ineffective. The physician's role in treating addiction includes prevention, diagnosis, brief intervention, motivational interviewing, referral, and follow-up care. An understanding of the biological reality of addiction allows physicians to understand addicts as having a brain disease. Further, the reality of effective pharmacological and cognitive-behavioral treatments for addiction allows physicians to be more optimistic in treating addicts. The challenge to the physician is to embrace the reality of addictive disease and fulfill his or her role in its treatment.