Takotsubo cardiomyopathy (TTC) is an acute heart failure syndrome classically characterized by hypocontractile apical and midventricular regions of the left ventricle, with a compensatory hypercontractile base. Available data support the hypothesis that TTC and atypical TTC-like disorders are primarily induced by catecholaminergic overstimulation, with epinephrine playing a crucial role. Knowledge from the available preclinical models should be used to guide the development of potential clinical trials in the most severe cases, where rates of acute morbidity and mortality are highest, and also to prevent recurrence in susceptible individuals.