Hepatitis C virus infection remains a significant health problem worldwide. The development of interferon-based therapies has led to increased success in eradicating this viral infection; however, no recent additions to the current treatment care regimen (peginterferon and ribavirin) have been made. Nonresponders to peginterferon/ribavirin make up a diverse patient population that can be difficult to manage. Through a better understanding of treatment response and viral kinetics, clinicians are employing altered dosing schedules to minimize the burden of viral illness. Consequently, clinicians can now manage nonresponders by providing supportive care and reserving retreatment for those most likely to respond to additional antiviral therapy, particularly when correctable factors from a previous treatment course with the potential for positive intervention have been identified. The decision for further medical management is based on clinical and laboratory parameters that have been shown to predict which patients will benefit most from another attempt at therapy.