The rise in tuberculosis (TB) has disproportionately affected specific populations. Historically, many patients with TB became iatrogenic opiate addicts through therapeutic use of these drugs for symptom control. Demographic trends reshaped the relationship between drug use and TB into one in which drug use became a risk factor for tuberculosis as a result of the overlap of epidemiological and social factors associated with both drug use and TB. The spread of human immunodeficiency virus infection has amplified the spread of TB among drug users. We review the epidemiology of TB in drug users as well as the factors relevant to screening and compliance in drug-using populations. Drug users constitute a high-risk group for whom screening, prevention of infection, diagnosis, and treatment pose particular challenges. The development of TB services capable of engaging drug users (those both in and out of drug treatment programs) has potential for disrupting a significant chain of rapid TB transmission.