Hepatitis C virus (HCV) has been the subject of intense research and clinical investigations due to its worldwide prevalence and major role in chronic liver disease. Like most RNA viruses, HCV circulates in vivo as a complex population of different but closely related viral variants, commonly referred to as a quasispecies. Recent studies suggest that ribavirin might exert an antiviral effect against HCV through both mutagenic effect and an impairment of RNA replication. The introduction of alpha interferon (IFN-alpha) plus ribavirin combination therapy was an important breakthrough in the treatment of chronic HCV infection. However, the rate of sustained virological response is still unsatisfactory, particularly in patients infected with HCV genotype 1. Viral persistence, a hallmark of HCV, may result from a dynamic control of the host response by the virus. In children with chronic HCV infection, the viral population is initially highly homogeneous, but diversifies during prolonged infection which seems to be a common event during chronic hepatitis C in childhood. Coinfection of human immunodeficiency virus 1 (HIV-1) patients by HCV can complicate the treatment of these patients with highly active antiretroviral therapy (HAART). HIV coinfection is associated with a decrease of HCV quasispecies variability, which appears to be reversed by effective HAART.