Hepatitis C virus (HCV) is a flavivirus that is endemic worldwide. Six genotypes are commonly recognized; a seventh rare genotype has been identified. Given its relative prevalence, this chapter focuses on genotypes 1 through 4. HCV is transmitted by blood-borne routes. Most acute infections are asymptomatic and progress to chronicity. Chronic infections are also asymptomatic until significant liver damage occurs. Pegylated alpha interferon plus ribavirin was the only treatment for many years. Highly potent, pan-genotypic, interferon-free direct-acting antiviral (DAA) regimens that cure >95% of clinical-trial subjects have been developed and will dramatically improve treatment. Routine diagnostics include serology, HCV RNA detection/quantification assays, and HCV RNA genotyping assays. Newer diagnostic tests include characterization of host genotype at loci upstream of IL28B that are associated with alpha interferon responsiveness, and HCV RNA tests to detect drug resistance mutations. Serology and HCV RNA detection/quantification tests are useful after a known exposure to identify acute infection. Serology is used to screen for chronic infection; seropositive individuals are then tested with HCV RNA detection/quantification assays to identify chronic infection. HCV genotype and viral load are determined prior to treatment initiation. In the pre-DAA era, HCV genotype was used to predict likelihood of response. It was also helpful to determine treatment regimen and therapeutic duration; these two uses will remain relevant for DAAs. Viral load testing during therapy will likely still be performed for assessment of medication compliance. IL28B genotype may retain some importance in predicting response rates in alpha interferon-containing regimens. Drug resistance tests thus far have limited applicability.