Cloning of the hepatitis C virus (HCV) genome was a tremendous advance in the development of tests for diagnosis and monitoring of HCV-infected patients. Serological tests, including enzyme-linked immunoassays and RIBA strip immunoblot assays, are primarily used to screen blood donations and to diagnose and confirm HCV infection. Tests for HCV RNA, including polymerase chain reaction (PCR)-based assays and the branched-DNA (bDNA) assay, are used for therapeutic monitoring and prognostics. Here, we present the development and future potential of these diagnostic tests. We also provide examples of how these tests are used to follow the progression of disease, select and adjust treatment protocols, and evaluate the efficacy of therapeutic regimens.