Because of the high rates of substance use disorders among the general and clinical populations, and the abuse potential of many medications commonly used in the treatment of neurologic illnesses, the treating neurologist must deal with drug misuse and abuse in practice. The most important tool neurologists must have in their arsenal is the ability to assess for and recognize substance use disorders in their patients. Any treatment plan developed for such patients must include ongoing management of substance abuse issues. After a substance use disorder is diagnosed, the neurologist must make proper referrals to adjunctive support interventions (Alcoholics Anonymous or Narcotics Anonymous) and chemical dependency specialists, and work closely and in collaboration with these components of the patient's overall treatment. The treating neurologist should be aware of the myriad neurologic sequelae of drug use, because most drugs of abuse, including alcohol, can have neurologic manifestations resulting from acute intoxication, acute withdrawal, or chronic use. Drug use (past and present) should be included in the differential diagnosis for any patient with an atypical constellation of symptoms or with isolated neurologic deficits. If the treatment of a neurologic condition requires the use of a potentially addictive substance, particularly when the patient has a history of substance use disorders, then the clinician must minimize the risk of addiction by giving the least addictive substances and developing a plan to manage the use of the drug throughout the treatment period.