Hepatitis C is the most common cause of liver disease in the dialysis patient. The prevalence of chronic hepatitis C determined by anti-HCV testing in this population ranges from 6% to 38%. Using second generation EIA assays, the prevalence of anti-HCV among patients participating in the 1997 National Surveillance of Dialysis Associated Diseases in the United States was 9.3%. Polymerase chain reaction testing for HCV RNA has shown that the prevalence of HCV infection can be as high as 20% to 30% of dialysis patients. The causes and source of infection in patients with chronic renal failure on hemodialysis are multiple. Before the introduction of routine screening of blood donors for anti-HCV, blood transfusions were an important risk factor for acquisition of hepatitis C. Other potential sources of infection include exposure to contaminated equipment and nosocomial routes such as patient-to-patient exposure. The risk of infection appears to correlate with the duration of hemodialysis and the number of transfusions. Interestingly, dialysate and buffers have been shown to be virus free even when used in hepatitis C infected patients. The natural history of chronic hepatitis C infection in patients with renal failure is not well characterized. Although persistent elevations in ALT levels occur in 12% to 50% of dialysis patients, the frequency of persistently normal ALT levels in HCV-infected dialysis patients appears to be higher than in HCV-infected patients without renal failure. Overt liver disease and liver failure rarely occur. The degree of inflammation in liver biopsies of renal failure patients is usually mild. Thus, progressive liver disease may be less common in patients with advanced renal disease but further studies are required to assess the true impact of hepatitis C infection in this high risk population. The impact of hepatitis C infection on morbidity and mortality of patients with end-stage renal disease remains poorly defined. Initial studies have failed to show a significant increase in mortality among HCV-infected hemodialysis or renal transplant patients within the first 5 years following transplantation. In contrast, recent studies with extended follow-up of renal transplant recipients suggest that hepatitis C infection may affect patient and graft survival during the second decade. Further studies are required to identify the mechanisms of infection of patients with end-stage renal disease and to define better treatment strategies for these patients before and after kidney transplantation.