The goal of this special issue is to present, in a comprehensive fashion, the latest data on Adult onset Still's Disease, within the broader context of the current concepts of autoinflammatory diseases and the immune mechanisms associated with them. A detailed review of Th-17 immune mechanisms and their association with autoinflammation by Waite and Skokos [1] is followed by two articles on potential disease biomarkers, serum ferritin, and IL-18 by Mehta and Efthimiou [2] and Colafrancesco et al., respectively. Mavragani et al. contributed with an up-to-date comprehensive report of Adult Still's, while Gurion et al. [3] go in depth over its pediatric counterpart, systemic JIA. Rossi-Semerano et al. examine whether both entities fall within the autoinflammatory spectrum and Giampietro et al. provide us with a detailed account of the leading treatments targeting IL-1, the common denominator.