Since the first description of interleukin‐1 (IL‐1) and the genesis of the field of cytokine biology, the understanding of how IL‐1 and related cytokines play central orchestrating roles in the inflammatory response has been an area of intense investigation. As a consequence of these endeavours, specific strategies have been developed to target the function of the IL‐1 family in human disease realizing significant impacts for patients. While the most significant advances to date have been associated with inhibition of the prototypical family members IL‐1α/β, approaches to target more recently identified family members such as IL‐18, IL‐33 and the IL‐36 subfamily are now beginning to come to fruition. This review summarizes current knowledge surrounding the roles of the IL‐1 family in human disease and describes the rationale and strategies which have been developed to target these cytokines to inhibit the pathogenesis of a wide range of diseases in which inflammation plays a centrally important role.