(1) Background: Hepatitis C is a high-prevalence disease, representing a global impact health problem. Lately, many changes have been made in treatment guidelines because of the commercialization of second-generation direct-acting antivirals due to their high effectiveness, few side effects and pangenotypic action. We address the pharmacological possibilities available and compare them with the current recommendations of the World Health Organization (WHO). (2) Methods: The search for articles was made through the PubMed database using different search strategies and we consulted technical data sheets of the treatments that have been included in the study. (3) Results: Combinations of “glecaprevir/pibrentasvir”, “sofosbuvir/velpatasvir” and “sofosbuvir/velpatasvir/voxilaprevir” have been recently incorporated. Phase II studies have shown that they are safe and effective therapies with very comfortable posologies and easy therapeutic adherence; furthermore, they suppose shorter treatment duration. Subsequently, phase III studies have shown they were effective for previously treated or compensated cirrhotic patients that previously had more complex treatment regimens. (4) Conclusions: These results suppose a simplification in Hepatitis C therapeutic approach, and open new study possibilities.