Clinical trials have unequivocally shown that cholesterol-lowering drugs decrease the risk of atherosclerotic cardiovascular disease in an exceptionally wide range of individuals. Yet, even when treated optimally according to current standards, many individuals still experience life-threatening ischemic events. Emerging experimental and clinical evidence strongly suggests that persistent inflammation is a major driver of this residual risk, which has opened the door to the application of anti-inflammatory drugs for cardiovascular disease prevention. Here, we review our current knowledge of the biology of interleukin-1β, a key regulator of inflammation in atherosclerotic plaque and the target of the first clinical trial to demonstrate that an anti-inflammatory drug can effectively reduce cardiovascular risk. We discuss the challenges faced by interleukin-1β inhibitors and other anti-inflammatory compounds in their translation to the clinical scenario, and identify other potential targets within this signaling pathway that hold promise in the cardiovascular setting., (Copyright © 2019 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)