Acute hepatitis C is often asymptomatic, frequently remains undiagnosed and frequently evolves to chronic hepatitis. Early, short-term interferon treatment is efficacious in acute hepatitis C, and so underscores the importance of an early diagnosis and the need to distinguish acute infection from acute exacerbation of chronic HCV infection. The gold standard for the diagnosis of acute hepatitis C is demonstration of conversion to anti-HCV positivity, HCV RNA positivity or both, events that frequently occur before the patient comes to medical attention. Several laboratory approaches to assist with early diagnosis of acute hepatitis C have been developed. Our studies, reviewed here, show that testing for antibody avidity and anti-HCV immunoglobulin M allow diagnosis in up to 90% of cases of acute hepatitis C.