Meningococcal disease remains an important cause of morbidity and death worldwide despite the development and increasing implementation of effective vaccines. Elimination of the disease is hampered by the enormous diversity and antigenic variability of the causative agent, Neisseria meningitidis, one of the most variable bacteria in nature. These features are attained mainly through high rates of horizontal gene transfer and alteration of protein expression through phase variation. The recent availability of whole-genome sequencing (WGS) of large-scale collections of N. meningitidis isolates from various origins, databases to facilitate storage and sharing of WGS data and the concomitant development of effective bioinformatics tools have led to a much more thorough understanding of the diversity of the species, its evolution and population structure and how virulent traits may emerge. Implementation of WGS is already contributing to enhanced epidemiological surveillance and is essential to ascertain the impact of vaccination strategies. This Review summarizes the recent advances provided by WGS studies in our understanding of the biology of N. meningitidis and the epidemiology of meningococcal disease.