Only vaccines based on genetic attenuation of virulence have reached clinical development thus far. The most advanced candidate is BPZE1, which has successfully completed six clinical studies, demonstrating safety, systemic and mucosal immunogenicity, and the ability to prevent or substantially reduce B. pertussis infection. If BPZE1 is eventually adopted for global use, it will likely be a major breakthrough in the ultimate control of pertussis, which has plagued humanity for centuries.