Meningococcal disease in most western countries is mainly caused by serogroup B. Despite the availability of successful meningococcal serogroup C conjugate vaccines, there is no effective vaccine against serogroup B. Efficacy trials with outer membrane vesicle (OMV) vaccines were ineffective and are complicated by the high variability of its main component, porin A. Several new approaches to either optimizing these OMV vaccines or searching for new, highly conserved antigens are therefore being investigated. The completion of the meningococcal genome sequence has provided new challenges. This review summarizes recent developments in the search for a broadly protective meningococcal serogroup B vaccine.