Liver disease is a major health problem for individuals with a history of injection drug use. This is mainly from the hepatitis C virus (HCV), with or without co-infection with HIV. HCV-associated liver disease takes decades to develop into cirrhosis, from which it can adversely affect health. HIV coinfection is among the factors that are often associated with liver disease progression, and efforts to understand liver disease progression in HIV-HCV coinfected patients remain important. Maintaining high CD4 counts and avoiding alcohol intake are associated with slower liver disease progression. Pegylated interferon and ribavirin combination therapy has the potential to clear HCV, which provides the strongest health benefit to patients affected by the virus, although this can be difficult to accomplish for many reasons. Steatosis, fat within the liver, may also have important pathological implications for liver disease related to HCV. Limiting liver disease progression in IDUs with hepatitis C may well be best accomplished through promoting their full utilization of health care.