Chronic hepatitis C (CHC) virus infection and associated hepatic diseases are still challenging, and the disease burden remains significant around the world. Overall treatment rates for the chronically infected patients have been “dismally poor” and that treatment completion of dual-therapy— pegylated interferon (PEG-IFN) and ribavirin (RBV) is suboptimal in the real-world clinical settings. The approval of first, second and next-generation direct-acting antivirals (DAAs) represents a major breakthrough in hepatitis C virus (HCV) therapeutics to treat CHC infected individuals. Such therapeutic regimens in a fixed dose combination (FDC) or along with RBV have proven their clinical efficacy against different HCV genotypes, and harder-to-treat special populations. We continue to see the development of novel pan-genotypic anti-HCV regimens with very high sustained virologic response (SVR; undetectable viral load at week 12 or at the end of therapy) rates, high barrier to drug resistance, low frequency of adverse events, and fewer drug-drug interactions as compared to some older RBV based triple DAA therapies. Oral interferon-free DAAs seem highly successful strategic treatment approaches against hepatitis C and impulse health policy makers to establish the treatment priorties and policies to reduce the rate of hepatitis C-related morbidity and mortality. This review article comprehensively overviews interferon-free anti-HCV regimens, which have totally shifted the treatment paradigms for hepatitis C with some additional benefits to galvanize our efforts to achieve the global goal of HCV elimination in near future.