The test to identify genomic RNA is the only tool currently available to directly evidence the presence of the hepatitis C virus (HCV) in infected subjects. In this review we examined the most commonly used qualitative and quantitative methods to detect HCV-RNA in serum or plasma, focusing particular attention on commercially available methods. Furthermore, we report the clinical conditions in which the viremia test is useful or even mandatory for the diagnosis of HCV infection, and comment on the usefulness of the test for monitoring patients in the course of antiviral therapy.