The results from clinical trials testing new direct-acting antivirals (DAAs) for chronic hepatitis C were the major focus of interest at the 2012 annual meeting of the European Association for the Study of the Liver. Besides triple combinations, in which any one of the new DAAs is given along with peginterferon-α/ribavirin, clinical trials exploring interferon-free oral regimens combining several DAAs attracted major attention. The good tolerance, broad hepatitis C virus (HCV) genotype activity, and high resistance barrier of sofosbuvir make this nucleotide analogue one of the most promising DAAs. Among HCV protease inhibitors, the safety, potency, and convenient dosing of simeprevir, asunaprevir, faldaprevir, and ABT-450/r were particularly highlighted. Among NS5A inhibitors, the good performance of daclatasvir encourages further clinical development. Finally, intriguing results were released about the role of interleukin 28B (IL-28B) polymorphisms using interferon-free regimens, indirectly supporting the role of innate immunity for clearing HCV definitively.