Since the advent of sensitive diagnostic blood tests for the detection of antibody to hepatitis C virus (HCV) in donors, there has been a large decline in the incidence of transfusion-related hepatitis. Globally, the infection has an estimated prevalence of 3%, with a prevailing 1% in Europe while varying geographically within a North-South gradient, ranging from around 0.5% in Northern countries to 2% in Mediterranean area. The incidence is very difficult to estimate accurately as many patients with acute HCV infection are asymptomatic and, thus, do not present for diagnosis. Data from the US report a fall in the annual occurrence of new cases per year from 230,000 in the late 1980s to approximately 35,000 in the 1990s. Therefore, a reduction in incident cases might eventually lead to lower prevalence of HCV infection. Although the incidence of viral infection may be decreasing, the prevalence of liver disease caused by HCV is on the rise. This is due to the significant lag, often 20 years or longer, between the onset of infection and clinical manifestation of liver disease. HCV can be transmitted by a variety of routes. It is most efficiently passed on by large or repeated percutaneous exposures such as through transfusions, transplantation from an infected donor or intravenous drug use. Transmission may also occur from contacts with infected subjects in the household, through perinatal and parenteral exposures in the health care setting. The risk of sexual transmission of HCV is low. Despite this knowledge, nearly half of infected patients do not have a history suggesting a parenteral route of acquisition. Since a prophylactic vaccine is hitherto not available, prevention becomes extremely important: identification of infected persons and of risk factors associated with acquiring HCV allow to develop strategies for preventing the spread of infection as well as its complications, and for planning appropriate care and support services.