Cytokines are key mediators of the immune system, and few have been more thoroughly studied than those of the IL-1 family. IL-1α and IL-1β are the founding members and now celebrate 25 years since their cloning. In that time, IL-1-directed research has illuminated many aspects of cytokine biology and innate immunity. The family is now recognized to include 11 total members, including IL-18 and IL-33, which are the topic of this review. These two inflammatory cytokines are expressed broadly, and their actions influence a variety of physiologic responses involved in inflammation and immunity. The purpose of this article is not to provide an exhaustive review of IL-18 and IL-33 but rather, to summarize what is known about their key functions and to provide perspective on their similarities and differences.