Chronic hepatitis C is a leading cause of clinical complications and mortality in individuals infected with human immunodeficiency virus (HIV). Approval for the first direct-acting antiviral (DAA) against the hepatitis C virus (HCV) has been eagerly awaited for treating patients coinfected with HIV/HCV. The use of first-generation HCV protease inhibitors is challenged by complicated dosing schedules, frequent serious toxicities, unwanted drug interactions, drug resistance, and high cost. First-generation DAAs will eventually be replaced by more potent, well-tolerated, and convenient agents. HIV/HCV co-infection will become restricted to individuals without proper access to health care.