TakoTsubo Syndrome (TTS) is a stress-induced cardiac disease characterized by temporary and segmental left ventricle dysfunction, typically involving the apex. Post-menopause women are more frequently affected. ECG and clinical features at presentation may be similar to those observed in acute coronary syndrome (ACS). However underlying pathomechanisms are completely different and, for what concerns TTS, extremely debated and not yet completely understood. Some hypotheses have been proposed during years, mostly regarding catecholamine-induced cardiotoxicity and microvascular dysfunction, usually following a trigger event which may be either “emotional” (primary TTS) or “physical” (secondary TTS). Additional modulators like neuroendocrine disorders (particularly hypothalamic-pituitary-adrenal axis dysfunction and estrogen drop in menopause) may play a crucial role in TTS onset. Despite being originally considered more benign than ACS, several studies have enlightened that TTS and STEMI are burdened by the same in-hospital mortality and complications. However, TTS and ACS complications somehow differ for what concerns incidence, the underlying mechanisms, and both long- and short-term outcomes. Full recovery in TTS requires weeks to months and cases of recurrences have been described, but no single clinical feature seems to predict subsequent episodes so far. By now, apart from inhibitors of the Renin-Angiotensin-Aldosterone System (RAASi), no drug has proved to be effective either in the acute or chronic phase in reducing mortality, improving outcome, or preventing recurrences.