The next decade will be a crucial period in the public health response to hepatitis C virus (HCV) infection. The rapid development of direct-acting antiviral therapy for HCV infection has brought considerable optimism to the HCV sector, with the realistic hope that therapeutic intervention will soon be more effective and offer shorter treatment duration. The initial phase of combination pegylated interferon, ribavirin and a protease inhibitor will be associated with increased toxicity and complexity of therapeutic management but, over the course of the decade, strategies including interferon-free combination direct-acting antiviral regimens with enhanced tolerability and simplified dosing schedules and monitoring protocols will emerge.