Hepatitis C is an important target for the development of disease management programs. Hepatitis C virus (HCV) infection is common and most infected individuals develop persistent infection. Although this is usually associated with chronic liver injury (chronic hepatitis C), the infection and liver disease may be unrecognized for years. Most patients are relatively asymptomatic and their illness remains clinically silent for at least 20 years after onset. In a substantial proportion of such individuals, the most widely available tests of the presence of liver injury, the serum aminotransferases, may be persistently normal. If unrecognized and untreated, chronic hepatitis C may lead to unfavorable outcomes including cirrhosis, the complications of end-stage liver disease, and hepatocellular carcinoma. These in turn sharply reduce health-related quality of life, lead to debilitating symptoms, decrease life expectancy by increasing premature death, and result in very high costs of care including the most expensive form of treatment - liver transplantation. In fact, end-stage liver disease due to chronic hepatitis C is now the single most common indication for liver transplantation in the US and Western Europe. Based on available data, the future illness and economic burden of chronic hepatitis C is likely to increase dramatically during the next few decades as currently infected, untreated individuals progress toward advanced liver disease. Unfortunately, treatment with the current agent of choice - the combination of interferon alfa and ribavirin - is difficult, expensive, and effective in only a proportion of patients. Nonetheless, computer-generated modeling studies indicate that current treatment diminishes the reduction in life expectancy expected in chronic hepatitis C and that cost-effectiveness ratios either fall within the bounds of other widely accepted medical interventions or are cost saving. Disease management programs in hepatitis C need to be designed to reduce unhealthy high risk behavior by education of the uninfected, promote health-seeking behavior such as the avoidance of alcohol in those infected, institute disease screening for those at risk with early confirmation of diagnosis, and initiate appropriate and effective treatment regimens, including actions designed to support adherence to treatment and appropriate follow-up. Advances in treatment such as the development of long-acting pegylated interferons which may enhance response rates, may be effective in advanced disease, and are well-tolerated should be incorporated into disease management programs when available. Disease management program design will require a multidisciplinary team approach and careful assessment of the effectiveness of these programs is needed.