Abstract: Injection drug users constitute the largest group of persons infected with the hepatitis C virus (HCV) in the United States, and most new infections occur in drug users. Controlling hepatitis C in the U.S. population, therefore, will require developing, testing, and implementing effective prevention and treatment strategies for persons who inject drugs. Fortunately, a substantial body of research and clinical experience exists on the prevention and management of chronic viral diseases among injection drug users. The need to implement interventions to stop the spread of HCV among drug users is critical. The capacity of substance-use treatment programs need to be expanded to accommodate all who want and need treatment. Physicians and pharmacists should be educated in how to provide access to sterile syringes and to teach safe injection techniques, both of which are lifesaving interventions. The treatment of hepatitis C in drug users requires an interdisciplinary approach that brings together expertise in treating hepatitis and caring for drug users. Treatment decisions should be made individually by patients with their physicians, based on a balanced assessment of risks and benefits and the patient’s personal values. Physicians should carefully assess, monitor, and support adherence and mental health in all patients, regardless of whether drug use is known or suspected. Research is needed to better understand how best to prevent and treat hepatitis C in substance users. In the meantime, substantial progress can be made if existing knowledge and resources are brought to bear.