Vaccination programs employing capsular-based meningococcal vaccines have proved successful in a variety of settings globally since first introduced over 40 years ago. Similar successes have been demonstrated using meningococcal vaccines for use against serogroup B (MenB) outbreak strains but the diversity of MenB strains has limited vaccine use outside targeted geographic regions. MenB continues to be a significant cause of outbreaks in adolescents and young adults, as recently demonstrated in university settings in the US (Princeton, New Jersey and Santa Barbara, California) and has the potential for hyperendemic disease levels such as currently experienced in Quebec and the United Kingdom. In adolescents, increased endemic disease rates and outbreak potential are likely associated with social behaviors putting individuals at risk for carriage acquisition and may explain regional and temporal variations in epidemiology. A protein-based, multi-component MenB vaccine (4CMenB) is currently licensed for use in 37 countries including EU/EEA countries, Australia, Canada, Chile, Colombia, Uruguay, and the US. In this article we review the most recent clinical trial data with 4CMenB with a focus on adolescents and young adults. The vaccine appears to have an acceptable safety profile and is well-tolerated in adolescents and young adults while providing robust, persistent levels of bactericidal antibodies considered protective for each of the four antigenic components of the vaccine. With the recent availability of this vaccine, health care providers have the first comprehensive opportunity to control meningococcal disease, a highly disruptive public health problem with a disproportionate impact on adolescents and young adults. (C) 2015 The Authors. Published by Elsevier Ltd.