The concept of autoinflammatory disorders was introduced by Daniel Kastner in 1999 (Michael McDermott was 1st author). Since then, characterization of these conditions has been continuously refined. After 20 years, McDermott, Caseley and Savic have advocated for a systems-based classification of the systemic autoinflammatory diseases (SAIDs) which defines the complex interplay of molecular mechanisms, and systems, at the heart of many monogenic and polygenic conditions.