The complexity and challenge of Hepatitis C virus (HCV) medication therapy call for a comprehensive and integrated approach in management. This article includes an appraisal of the current state of the science in HCV management and the various models that support treatment completion and adherence. The patient undergoing HCV therapy may experience a wide range of symptoms such as anemia, depression, fatigue, and flu-like symptoms. These can constantly confront the patient's adherence and compliance with treatment. The article includes an analysis of the strengths, weaknesses, and limitations of the evidence. Future directions in research were also identified.