Takotsubo cardiomyopathy (TC) is characterized by reversible ventricular dysfunction, not limited to the distribution of an epicardial coronary artery. A disease primarily afflicting post-menopausal women, it is frequently mistaken for acute anterior wall myocardial infarction. Alternatively called Stress Cardiomyopathy, physical or emotional triggers are identified in only three fourths of TC patients. Long considered a benign condition, recent findings suggest poor short term prognosis similar to acute coronary syndrome (ACS). Despite the widely recognized pathophysiological role of catecholamine excess, its diagnostic role is uncertain. TC is suspected based on typical wall motion abnormalities in ventriculogram or echocardiogram. Several additional electrocardiographic, laboratory and imaging parameters have been studied with the goal of clinical diagnosis of TC. While several clinical clues differentiate it from ACS, a clinical diagnosis is often elusive leading to avoidable cardiac catheterizations. Natriuretic peptides (NPs), a family of peptide hormones released primarily in response to myocardial stretch, play a significant role in pathophysiology, diagnosis as well as treatment of congestive heart failure. TC with its prominent ventricular dysfunction is associated with a significant elevation of NPs. NPs are elevated in ACS as well but the degree of elevation is typically lesser than in TC. Markers of myocardial injury such as troponin are usually elevated to a higher degree in ACS than in TC. This differential elevation of NPs and markers of myocardial injury may play a role in early clinical recognition of TC.