Our objective is to provide a state-of-the-art review on hepatitis C (HCV) and the human immunodeficiency virus (HIV) in injection drug users (IDUs), highlighting important clinical issues. We performed a literature review from the MEDLINE database for research from 1966 to 2003, with an emphasis on recent consensus documents. Of the estimated 15 million illicit drug users in the U.S., approximately 1.0 to 1.5 million inject drugs. IDUs are at significant risk of contracting HCV and HIV, with IDUs accounting for 60% of new HCV cases and 25% of new HIV infections. It is a major risk factor for HCV/HIV coinfection, which significantly impacts on each disorder's progression. It appears that treatment response in IDUs with HCV or HIV is similar to non-IDUs with these viruses and that medication adherence and treatment outcomes are optimized when linked with substance abuse treatment. Providers caring for patients who are or were IDUs must be aware of the management of these diseases and make efforts to integrate their medical care with the treatment of their substance abuse.