The availability of the new generation of direct-acting antiviral (DAA) therapies for the treatment of chronic hepatitis C virus (HCV) infection has completely transformed the HCV therapeutic landscape. Current regimens provide pan-genotypic coverage that are of short duration, safer, and are highly effective than prior generations of HCV therapeutics. While data from clinical trials and real-world experience continue to demonstrate similar and high sustained virologic response (SVR) rates, the successful implementation of the HCV cascade-of-care including screening, confirmation of active infection, treatment initiation and successful completion of therapy among more challenging populations, such as the underserved populations who are also disproportionally affected by HCV, remains vital to HCV eradication efforts.