The introduction of direct acting antiviral agents (DAAs) will markedly change treatment options for individuals who have a chronic HCV infection. Within the next few months, licensing of two HCV protease inhibitors (boceprevir and telaprevir) for the treatment of patients with chronic hepatitis C as part of a triple therapy with PEG-IFN-α and ribavirin is anticipated in the USA, Europe and many other countries. Final results of pivotal phase III clinical trials in previously untreated and treatment-experienced patients with HCV genotype 1 infection were presented at the Annual Meeting of the American Association for the Study of the Liver 2010 held in Boston, MA, USA, and at the Annual Conference of the Asian Pacific Association for the Study of the Liver 2011, held in Bangkok, Thailand. This article summarizes the results of these phase III trials in consideration of accumulating data on important baseline and on-treatment predictive factors for treatment response, such as the host IL28B genotype and the rapid virologic response; the introduction of these new therapies into clinical practice is also covered. Furthermore, preliminary data on the combination of different classes of DAAs, such as HCV protease inhibitors and HCV polymerase inhibitors, without interferon α are discussed.