Advances in treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) have led to high cure rates of treated patients. Although rates of sustained virologic response of approximately 95% have been achieved, a large number of patients still fail treatment, even with drug combination regiments. A high percentage of these treatment failures are due to the emergence of resistance-associated variants (RAV). Chronic HCV infection consequently will continue as a leading cause of cirrhosis and hepatocellular carcinoma, which are major indications for liver transplantation.