HCV NS3 serine protease mediates the cleavage of the HCV polyprotein to release the functional proteins that are essential for viral propagation. The inhibition of NS3 protease activity is expected to block HCV replication in infected host cells, and therefore protease inhibitors are a potential new treatment strategy for HCV. Several novel HCV protease inhibitors have been discovered, of which some have been clinically proven to be effective in achieving sustained virological response in patients with HCV genotype 1 at rates higher than those observed with the standard of care. This review focuses on the recent advances in the development of HCV protease inhibitors.