Takotsubo cardiomyopathy is an acute stress-induced heart failure syndrome for which the exact pathogenic mechanisms are unclear, and consequently, no specific treatment exists. In an experimental model of stressinduced takotsubo-like cardiomyopathy, the authors describe the temporal course of a chronic inflammatory response post-induction, with an initial early influx of neutrophils into myocardial tissue followed by macrophages that are typical of a proinflammatory M1 phenotype, and a nonsignificant increase in systemic inflammatory cytokines. Post-mortem myocardium from the more complex clinical takotsubo patients share features of the study's experimental model. These findings suggest modulators of inflammation could be a potential therapeutic option. (J Am Coll Cardiol Basic Trans Science 2018;3:766-78) © 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.