Inflammasome is a very important signaling platform sensing a variety of triggers of the innate immune system. Inflammasome promotes the production of important pro-inflammatory cytokines such as IL-1β and IL-18. Tight control of inflammasome activity is, therefore, essential and occurs at multiple levels. The activation of inflammasome pathways is linked to the pathogenesis of various prevalent disorders including cardiovascular disease such as atherosclerosis, ischemic injury, cardiomyopathy, and Kawasaki disease. The study of the inflammasome in the cardiovascular system has led to the identification of important triggers and endogenous modulators, and to the exploration of new treatment strategies based on the inhibition of inflammasome activation or its end products, i.e., IL-1β and IL-18. In summary, the discovery of the inflammasome has greatly advanced our understanding of how the innate immune system interferes with cardiovascular disease development and progression, and targeting inflammasome provides new avenues for the treatment and management of cardiovascular diseases.