The interleukin (IL)‐1 family of cytokines is currently comprised of 11 members that have pleiotropic functions in inflammation and cancer. IL‐1α and IL‐1β were the first members of the IL‐1 family to be described, and both signal via the same receptor, IL‐1R. Over the last decade, much progress has been made in our understanding of biogenesis of IL‐1β and its functions in human diseases. Studies from our laboratory and others have highlighted the critical role of nod‐like receptors (NLRs) and multi‐protein complexes known as inflammasomes in the regulation of IL‐1β maturation. Recent studies have increased our appreciation of the role played by IL‐1α in inflammatory diseases and cancer. However, the mechanisms that regulate the production of IL‐1α and its bioavailability are relatively understudied. In this review, we summarize the distinctive roles played by IL‐1α in inflammatory diseases and cancer. We also discuss our current knowledge about the mechanisms that control IL‐1α biogenesis and activity, and the major unanswered questions in its biology.