Pro-inflammatory cytokines are crucial for fighting infection and establishing immunity. Recently, other proteins, such as danger-associated molecular patterns (DAMPs), have also been appreciated for their role in inflammation and immunity. Following the formation and activation of multiprotein complexes, termed inflammasomes, two cytokines, IL-1β and IL-18, along with the DAMP High Mobility Group Box 1 (HMGB1), are released from cells. Although these proteins all lack classical secretion signals and are released by inflammasome activation, they each lead to different downstream consequences. This review examines how various inflammasomes promote the release of IL-1β, IL-18 and HMGB1 to combat pathogenic situations. Each of these effector molecules plays distinct roles during sterile inflammation, responding to viral, bacterial and parasite infection, and tailoring the innate immune response to specific threats.