Hepatitis C virus (HCV) infection is a major health burden and associated with substantial morbidity and mortality. However, the disease often remains underdiagnosed and untreated. The treatment of HCV infection has evolved dramatically with the introduction of novel, interferon-free therapies that are now able to achieve high cure rates. However, improved and more effective strategies for controlling the high costs of managing patients with HCV, especially in light of the shifting treatment paradigm, need to be developed. This article, the second in a series of 3 focused on hepatitis C, will discuss the diagnosis and management of HCV infection, including treatment recommendations from practice guidelines and emerging agents to treat HCV, and provide suggestions for incorporating these options into treatment algorithms.