Neisseria meningitidis is a commensal of human nasopharynx and humans are the only known reservoir and host of this bacterium. It is also known as a dangerous and devastating pathogen, and infection with N. meningitidis may lead to rapidly progressing septicemia or meningitis. These severe infections, called invasive meningococcal disease (IMD), are one of the major public health threats worldwide. IMD may occur sporadically, but also in outbreaks, epidemics, and pandemics. Most of the IMD cases in the world are caused by isolates of genetically related groups, clonal complexes (CC), including those with special epidemiological significance called hyperinvasive clonal complexes. It is still unknown why some of them may persist for decades, whereas other are quickly replaced and disappear. As a consequence, the epidemiological situation of IMD is variable worldwide and greatly depends on the emergence and widespread of clones belonging to hyperinvasive clonal complexes. Their occurrence has serious implications for health policy, requiring often mass immunization campaigns. Paradoxically, alarming situations caused by hyperinvasive CCs stimulated the development and introduction of new vaccines against meningococci. Despite the unquestionable success of these vaccines, isolates of hyperinvasive clones constitute a permanent public health threat, because they are constantly circulating and able to modify their antigenic profiles to escape the host immune response. Therefore, continuous monitoring of meningococcal isolates including thorough molecular typing is indispensable and fundamental for taking appropriate preventive measures.