The genetic regulation of the host response to infection is crucial for understanding susceptibility to and outcome of meningococcal disease. The initial host response depends on the innate immune system, after which specific immunity is attained when antibodies from the adaptive immune system appear. The comparison of genetic markers in patients who have suffered from the disease, their families, and appropriate control populations thus identifies components of the host response that are key to combat meningococcal infection. A similar reasoning can be followed when studying susceptibility to or when studying outcome of meningococcal disease. A better understanding of the host response at a molecular level also allows for estimating individual risk. This accumulating knowledge can be used to develop new preventive and therapeutic interventions and to vary these strategies dependent on risk profiles.