Chronic hepatitis C virus (HCV) infection affects millions of individuals and is a significant cause of chronic liver disease and cirrhosis. Early treatment regimens relied on an immune-mediated response caused by interferon and only recently have medications acting directly on viral structures been discovered. In December 2013, two new medications, sofosbuvir and simeprevir, were approved by the US Food and Drug Administration (FDA) for treatment of chronic hepatitis C. This article reviews the approved treatment protocols for these two new medications and the clinical trials that fueled their development.