Methods and compositions for the efficient and accurate determination of susceptibility of a hepatitis C virus (HCV) or HCV population to interferon (IFN), ribavirin (RBV), nucleoside inhibitor (NI), 2'C-methyl adenosine (2'CMeA), sofosbuvir (SOF), or non-nucleoside inhibitor A or B (NNI-A or NNI-B) are provided. The methods may involve determining the genotype of the HCV or the phenotype of the HCV with respect to IFN, RBV, NI-1, 2'CMeA, SOF, NNI-A, or NNI-B susceptibility. The methods may further include the selection of a suitable treatment based on the genotype or phenotype determined.