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Given the global importance of chronic hepatitis C virus infection as a major health burden, there is still a need for treatment options that are more efficient, safer, simpler, more convenient and preferably interferon-free. Sofosbuvir (GS-7977; formerly PSI-7977) is a direct-acting antiviral agent that has met many of these attributes. This novel nucleotide analogue has demonstrated a consistently potent antiviral activity across several hepatitis C virus genotypes, and has been found to be safe and well tolerated when administered alone or with ribavarin +/- pegylated interferon. The clinical data evaluating the safety, tolerability and antiviral activity of sofosbuvir in various treatment regimens are presented in this article. Sofosbuvir is a major breakthrough in the care of HCV infection, making it possible that thousands of HCV infected patients around the world achieve cures, and preventing HCV associated morbidity and mortality.