Inhibitors of the NS5A replication complex of the hepatitis C virus (HCV) are a novel family of antiviral medications that have transformed the management of chronic hepatitis C infections. By aiding in the formation of the viral RNA replication complex, the NS5A protein is essential for the viral replication process. This crucial stage in the HCV life cycle is disrupted by NS5A inhibition, thereby preventing viral replication and lowering viral loads in infected people. Ledipasvir was one of the first NS5A replication complex inhibitors to be approved, and it showed significant success in treating different HCV genotypes when coupled with sofosbuvir. Due to its high rate of success and manageable side effects, this combination therapy became the norm in medical practice. Later, additional NS5A inhibitors were created and added to the arsenal of hepatitis C medications, including daclatasvir, velpatasvir, and pibrentasvir. Patients tolerate these inhibitors well and they are often given orally. They provide a strong and targeted method of action against HCV, lowering the possibility of viral resistance. In order to obtain even greater cure rates and to account for the genetic variability of the virus across diverse patient groups, NS5A replication complex inhibitors are frequently used in combination with other direct-acting antiviral medications that target various stages of the HCV life cycle. Hepatitis C treatment has changed as a result of the success of NS5A replication complex inhibitors, which have made it feasible to achieve sustained virological response (SVR), effectively treating the virus in the majority of patients. This development in antiviral medication has greatly decreased the burden of liver disease, cirrhosis, and hepatocellular carcinoma linked to chronic HCV infections in addition to improving the quality of life for people with hepatitis C. A great feat in the area of medicine, the creation and ongoing improvement of NS5A replication complex inhibitors have cleared the road for the elimination of hepatitis C worldwide.