In just five years, hepatitis C has changed from a difficult-to-treat chronic condition to one that is readily cured by a short course of medication. Medical breakthroughs have now created the possibility of eliminating the transmission of HCV, but also bring a new challenge for the health system—how to identify individuals carrying the hepatitis C virus (HCV), and how to pay for life-saving treatments. This Issue Brief reviews recent evidence on the cost-effectiveness of screening and treatment strategies, and makes the case for universal, one-time HCV screening for all US adults.