Chronic hepatitis C virus (HCV) is the most common blood-borne pathogen in the United States. HCV disproportionately affects Veterans Affairs (VA) health-care users: 174,302 HCV-infected veterans were in VA care in 2013, making the VA the world's largest HCV care provider. This systematic review identified 546 articles related to HCV in the VA. After assessment by 2 independent reviewers, 28 articles describing prevalence and treatment of HCV in VA users ultimately met inclusion criteria. Most VA patients currently living with HCV infection were born between 1945 and 1965 and were infected with HCV between 1970 and 1990. To prevent HCV-related complications such as cirrhosis, hepatocellular carcinoma, and death, medical personnel must identify and treat HCV. However, antiviral therapy has historically been limited by medication side effects, contraindications, and patient acceptance. Although treatment initiation rates are higher in the VA than in the general United States, only 23% of VA HCV patients have received treatment and, of those, only a minority were cured. Recent development of more effective and tolerable antiviral agents represents a major pharmacological breakthrough. Eradication of HCV is theoretically possible for the majority of HCV patients for the first time, although new barriers, such as high drug costs, may limit future uptake.