Autoinflammatory syndromes are often the result of genetic mutations that ultimately compromise neutrophils, macrophages and other cells of the innate immune system. Rather than showering sufferers with broad immunosuppressives, a more satisfactory response can frequently be obtained using select anti-inflammatory drugs like anti-TNF or anti-IL-1β. A similar inappropriate innate activation is now commonly observed in susceptible individuals who have progressed to acute respiratory distress after SARS-CoV-2 infection. In trying to fight back against a pathogen surveillance system that has gone haywire, many are now asking how we might do better.