Inflammasomes are cytosolic multiprotein complexes that can proteolytically activate caspase-1. Activated caspase-1 is needed for the maturation and secretion of interleukin (IL)-1beta and IL-18. In the past decade, there has been tremendous progress in our knowledge of inflammasome function and IL-1 signaling, mainly in cells of the innate immune system, such as monocytes, macrophages, neutrophils, and dendritic cells. Because nonimmune cells, including keratinocytes, synovial cells, or astrocytes, can form an interface between the body and the environment or a defined compartment (brain, joint), they are important guardians for the detection of danger signals and the consecutive initiation of an inflammatory response. They are present in anatomical compartments that are less accessible to myeloid cells and thus can fulfill tasks usually performed by residential macrophages. This review focuses on recent progress in our understanding of the processing and functional role of IL-1 in epithelial, mesenchymal, and neuronal cells and in conditions such as tissue repair.