Although knowledge of the molecular biology of the hepatitis C virus is rapidly evolving, current therapeutic strategies remain suboptimal for most patients with chronic hepatitis C. It is hoped that with information derived from virologic variables, therapy can be tailored to individual patients, offering them the greatest likelihood of response or preventing the unnecessary use of costly and occasionally unpleasant medications when treatment failure is deemed probable. Genotyping and quantitation of hepatitis C virus have provided great insights into the pathogenesis of chronic hepatitis C. Retrospective studies have demonstrated that hepatitis C virus genotyping and viral burden may play some role in disease progression and response to therapy. With the widespread availability of these tests, it is important to try to develop a rational plan for their use that will provide information in a manner that is both cost-effective and relevant to clinical decision making for the individual patient. At this point, the utility of measuring hepatitis C virus RNA levels and genotyping in making decisions about treatment regimens or monitoring therapy in daily clinical practice is continually evolving.