According to the third National Health and Nutrition Examination Survey (NHANES), 3.9 million of the U.S. civilian population have been infected with hepatitis C virus (HCV), of whom 2.7 million (74%) have chronic infection. Hepatitis C virus infection is most common among non-Caucasian men, ages 30 to 49 years. Moreover, the prevalence of antibody to hepatitis C virus in groups not represented in the NHANES sample, such as the homeless or incarcerated, may be as high as 40%. The age-adjusted death rate for non-A, non-B viral hepatitis increased from 0.4 to 1.8 deaths per 100,000 persons per year between 1982 and 1999. In 1999, the first year hepatitis C was reported separately, there were 3,759 deaths attributed to HCV, although this is likely an underestimate. There was a 5-fold increase in the annual number of patients with HCV who underwent liver transplantation between 1990 and 2000. Currently, more than one third of liver transplant candidates have HCV. Inpatient care of HCV-related liver disease has also been increasing. In 1998, an estimated 140,000 discharges listed an HCV-related diagnosis, accounting for 2% of discharges from non-federal acute care hospitals in the United States. The total direct health care cost associated with HCV is estimated to have exceeded $1 billion in 1998. Future projections predict a 4-fold increase between 1990 and 2015 in persons at risk of chronic liver disease (Le., those with infection for 20 years or longer), suggesting a continued rise in the burden of HCV in the United States in the foreseeable future. (HEPATOLOGY 2002;36:S30-S34.) n July 2000, the United States Surgeon General declared that hepatitis C represents a "silent epidemic." I Indeed, hepatitis C is the most common chronic bloodborne infection in the United States, affecting almost 3 million Americans. This review focuses attention on the disease burden associated with hepatitis C virus (HCV) infection. The term, "disease burden," encompasses several aspects of the impact of a disease on the health of a population, ranging from the frequency of the disease, as measured by incidence and prevalence, to its effect on (1) longevity, such as mortality rate and years of life lost because of premature death; (2) morbidity, including impairment in health status and quality of life as well as the need for health care; and (3) finance, including