A hallmark of RNA viruses is their extreme genetic diversity. Within an individual, the hepatitis C virus (HCV) exists as a population of distinct but closely related viral variants, termed the “viral quasispecies.” These variants may display divergent replicative capacity, cell tropism, immunologic escape, and antiviral-drug resistance. Coinfection with 2 or more distinct HCVs has been frequently documented. Moreover, several cases of HCV superinfection have been reported recently. However, few data are available regarding the clinical consequences of coinfection and superinfection, although these phenomena have important implications for HCV vaccine design and development, as well as for the efficacy of HCV therapeutic agents.