Meningococcus B is an uncommon but life-threatening disease with potentially severe sequelae and a high case-fatality rate. Epidemiology is unpredictable due to strain evolution and outbreak potential. Development of broadly effective MenB vaccines was complex due to challenges specific to the use of the capsular polysaccharide. Through “reverse vaccinology” it was possible to discover novel antigens from the genome, which were then used for the development of a broadly protective vaccine against meningococcus B, 4CMenB, which was impossible before. It is based on four components: Neisseria adhesin A (NadA), factor H binding protein (fHbp) and the Neisserial Heparin Binding Antigen (NHBA), in combination with outer membrane vesicles (OMV) from the New Zealand outbreak strain, expressing porin A protein (PorA) P1.4. The vaccine is licensed in more than 40 countries, in infants from two months of age in Europe and in several countries worldwide, and in 10–25 years of age in the United States. Each of the 4CMenB antigens induces bactericidal antibodies that mediate killing of multiple strains even synergistically. One or more of the 4CMenB antigens are present and conserved also in non-B strains and in gonococcus, suggesting that immunization with 4CMenB may provide protection also against other serogroups and gonococcus. The implementation of 4CMenB in national programs is providing evidence on the impact of 4CMenB on meningococcal and gonococcal diseases.