Charles Dinarello began his career in 1971 with the objective to purify the endogenous fever-producing protein then called “leukocytic pyrogen.” Six years later, he published the isolation of a single human protein that produced fever in rabbits, now termed interleukin-1 beta (IL-1β). When injected into humans, IL-1β was highly inflammatory and produced fever and a rise in neutrophils. In 1981, he described the existence of a naturally occurring inhibitor of IL-1 activity, now known as the IL-1 receptor antagonist (IL-1Ra). In 1999, he discovered the IL-18 binding protein (IL-18BP). In 2010, his group elucidated the function of the elusive member of the IL-1 family, IL-37. Prof. Dinarello’s career continues to focus on the role of inflammatory cytokines as mediators of acute and chronic diseases. His goal is to understand the role of IL-1 and other members of the IL-1 family to provide improved and more specific treatments.