The Infectious Diseases Society of America and the American Association for the Study of Liver Diseases have collaboratively developed evidence-based guidance regarding the diagnosis, management, and treatment of hepatitis C virus (HCV) infection since 2013. A panel of clinicians and investigators with extensive expertise in infectious diseases or hepatology specific to HCV infection periodically reviews related evidence and update existing recommendations or introduce new recommendations based on such evidence. This update focuses on the changes to the guidance since the update in 2020, including recommendations for extensive universal screening, simplified treatment and testing regimens, treatment of poor compliance, and management of unique and key populations such as children aged <3 years and patients undergoing transplantation.