Various genes regulate the intensity of the inflammatory and coagulation response to infection and therefore might determine the severity and outcome of meningococcal disease. We systematically reviewed the published work for case–control studies on the influence of host genetics on severity and outcome in meningococcal disease and identified 27 studies including 7245 patients, with an overall mortality of 10% (range 1–19%). Despite flaws in the methods of the studies there was a clear association of host genetics with mortality and severity in meningococcal disease. Polymorphisms in SERPINE1 (odds ratio [OR] 2·23, 95% CI 1·48–3·35), IL1RN (OR 1·85, 95% CI 1·25–2·76) and IL1B (OR 1·81, 95% CI 1·09–2·97) were associated with mortality in our meta-analyses. In conclusion, gene variation influences severity and mortality in meningococcal disease. Polymorphisms might have potential as prognostic markers or to determine tailor-made adjunctive therapy. Carefully designed, prospective, whole-genome association studies and randomised clinical trials of treatments in specific genetic subgroups are needed.