OBJECTIVES: Hepatitis C virus (HCV) treatments have been improved by the availability of highly effective and well-tolerated interferon-free therapies. This study probes the impact of such therapies on the role of primary care physicians (PCPs) in diagnosis, referral, and treatment of HCV patients who have historically been treated by gastroenterologists and hepatologists. METHODS: In the U.S., 100 PCPs, 51 specialists (44 gastroenterologists, 7 hepatologists), and 30 Managed Care Organization (MCO) pharmacy directors/medical directors (PDs/MDs) were surveyed to assess PCP knowledge of and involvement in HCV diagnosis and screening, referral patterns, and treatment options. RESULTS: Survey results identify referral to specialists as a notable barrier to accessing care. Some 77% of PCPs who follow-up with patients they refer to HCV specialists estimate that 24% are lost to follow-up. Similarly, 73% of specialists report having PCP-referred patients who missed their exam, and these specialists estimate that 15% of all PCP-referred patients “drop off”. In anticipation of multiple new HCV therapies reaching the major markets, several professional societies have collaborated to develop expert-curated, regularly updated guidelines providing clinical recommendations for diagnosing and treating HCV patients (www.hcvguidelines.org). Among surveyed PCPs, 74% were unaware of these guidelines; however, once informed, 63% of all PCP respondents indicated greater comfort with prescribing treatments recommended by these guidelines. Furthermore, 63% of MCO PDs/MDs and 98% of HCV specialists surveyed reported feeling more comfortable with PCPs prescribing these recommended treatments. CONCLUSIONS: The substantial decline in the cascade of care from PCP referrals to specialists suggests that educating PCPs on new interferon-therapies presents an opportunity to maximize retention in care and accelerate efforts to identify undiagnosed cases. Survey responses from PCPs, as well as specialists, and MCO PDs/MDs suggest that practical, regularly updated clinical guidelines prepared by international experts could provide a common framework for educational outreach efforts to PCPs.