Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the general U.S. population and 5-10% of veterans who use Department of Veterans Affairs medical services. Chronic HCV is clearly linked to the development of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease requiring liver transplantation. The consequences of HCV infection constitute a significant disease burden and demonstrate the need for effective medical care. Treatment of chronic HCV is aimed at slowing disease progression, preventing complications of cirrhosis, reducing the risk of HCC, and treating extrahepatic complications of the virus. As part of a comprehensive approach to HCV management, antiviral therapy with peginterferon alfa combined with ribavirin is the current standard of care. Antiviral therapy should be provided to those individuals who meet criteria for treatment and who are at greatest risk for progressive liver disease. Many of these patients may have comorbid medical and psychiatric conditions, which may worsen while on antiviral therapy. Current antiviral regimens are associated with significant adverse effects that can lead to noncompliance, dose reduction, and treatment discontinuation. To overcome these barriers and to address these issues, it has become crucial to facilitate a multidisciplinary team who can respond to and provide HCV-specific care and treatment. Screening for HCV, preventing transmission, delaying disease progression, ensuring appropriate antiviral therapy, and managing treatment-related adverse effects can improve patient quality of life, treatment adherence, and ultimately, improve patient outcomes.