Hepatitis C virus (HCV) is the leading cause of chronic liver disease, surpassing hepatitis B virus and alcohol. The paradigm for treating HCV has radically changed over the last 20 years. The tolerability and duration of treating HCV patients was altered fundamentally by the emergence of modern and more efficacious treatment regimens and plans. Nevertheless, the risk of developing serious adverse reactions, including those due to drug–drug interactions, remains high. Currently, eight drugs are approved for treating HCV and avoid the use of interferons. The present article reviews these drugs with respect to their efficacy and safety for use in patients with various HCV genotypes. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.