Current treatment for chronic hepatitis C is expensive, is often accompanied by burdensome side effects, and, sadly, fails in almost half of cases. The ability to predict such failures prior to treatment could save a great deal of pain and expense for the patient with HCV. In this issue of the JCI, Aurora and colleagues describe the development of genetic markers predictive of treatment response based on a study of viral sequence variation (see the related article beginning on page 225). Genome-wide covariation analyses of pretreatment virus sequences from 94 patients showed distinct patterns of mutations strongly associated with the ultimate success or failure of treatment. Such analyses suggest markers predictive of response to therapy and may lead to new insights into the underlying biology of hepatitis C.