Reading the rapidly expanding data on Takotsubo syndrome (TTS), one can sense that some stagnation has been creeping into the field. All the case studies and review articles appear identical and stereotypical in their exposition, almost “carbon copies” in the particulars they have reported, the specific references they have cited, and the pathophysiologic speculations they have attempted. Perusing the most recent entries, of the 1,607 reports retrievable as of April 14, 2013 in PubMed, using the search term “Takotsubo” ( http://www.ncbi.nlm.nih.gov/pubmed/?term=takotsubo ), one will be exposed to a fixed litany of facts and hypotheses, ending with the conclusion that we have a number of conundrums of an affliction with an unknown pathophysiology. Perhaps the following “thoughts outside the box” will be worth pursuing and could provide a needed spur to reenergize the field in new directions. First, it is unknown whether a change occurs in the topography of the left ventricular (LV) wall contraction abnormalities in individual patients during the acute phase of the clinical presentation of TTS. Second, we do not know whether the LV basal hypercontractility is more intense in the hyperacute phase of the illness than later, during the first day of hospital admission. Third, it is unknown whether gradations of the apical “ballooning” (dyskinesis) occur during the acute course of TTS in individual patients. Fourth, do all patients with TTS experience a LV intraventricular pressure gradient during the hyperacute phase of the illness and are such gradients dynamic in nature, starting as very intense and ending, in most patients, completely abolished? Fifth, we wonder whether the ST-segment elevation on the electrocardiogram is temporally associated with the LV apical “ballooning,” with simultaneous conversion from dyskinesis to akinesis, in terms of the wall contraction abnormalities, and from ST-segment elevation to T-wave inversion with QTc prolongation, in terms of the electrocardiogram. Sixth, do these conversions result from the development of myocardial edema, with resultant LV regional stiffening and akinesis? Seventh, is it possible that the apical “ballooning,” modest biomarker release, ST-segment elevation, myocardial edema, microcirculation abnormality, pathoanatomic, histochemical, and inflammatory myocardial changes, and sympathetic nervous system denervation result from the mechanical stress engendered by a LV hypercontractile base on the mechanically paralyzed LV apex and LV midventricular wall? Eighth, do some patients with TTS reach resolution within hours after the onset of the illness? Ninth, it is unknown whether mild or forme fruste cases of TTS exist. Tenth, are “TTS components” superimposed on the clinical phenotype of other common illnesses, including acute coronary syndromes? Eleventh, could cases of sudden cardiac death, either fatal or with successful resuscitation, in particular in men, be due to TTS? Finally, is TTS at the root of unexplained transient T-wave inversions and/or QTc prolongation on the electrocardiogram or wall contraction abnormalities on the echocardiogram, in particular, in postmenopausal women? Researching these speculations and implementing more often than is currently the case, electrocardiography, echocardiography, and cardiac magnetic resonance imaging might unravel the TTS conundrum sooner.