Substance use is highly prevalent among patients presenting to emergency departments (EDs). Substance use complicates differential diagnosis of the ED patient, as substance use can mimic a variety of psychiatric syndromes. Chronic drug and/or alcohol use significantly increases the likelihood that a person will use an ED for medical treatment. The drugs of abuse and intoxication include alcohol, opiates, sedative hypnotics, stimulants, hallucinogens and dissociative agents, inhalants, and cannabinoids. Drug intoxication is commonly involved in ED visits, and patients may present with a variety of medical and psychiatric complaints. Drug intoxication complicates clinical presentation and can lead to prolonged ED length-of-stay, deployment of resources, including the use of restraints in severe intoxication syndromes, and creates a challenge for disposition and treatment.