Chronic hepatitis C infection remains a major global public health burden associated with substantial morbidity and mortality. Recent advances in antiviral therapy with the US Food and Drug Administration (FDA) approval of the oral protease inhibitors boceprevir and telaprevir introduce a new era of treatment for hepatitis C based on directly acting antiviral agents, which are associated with significant improvements in viral eradication rates in combination with pegylated interferon plus ribavirin. Newer classes targeting the hepatitis C virus (HCV) protease, polymerase, NS5A, and other components of the viral genome demonstrate great promise to further enhance viral eradication with superior efficacy, improved tolerability, shorter duration of therapy, and diminished requirement for interferon. Current and future strategies for HCV pharmacotherapy are reviewed.