Eosinophilic coronary monoarteritis is an unfamiliar cause of acute myocardial ischemia. Most commonly, it presents as a left-sided chest pain or sudden death in middle-aged women with no traditional risk factors for coronary artery disease. Because the abrupt onset leaves almost no time for intervention, the symptoms readily lead to death, and most cases are diagnosed at necropsy. Dissection of the coronary artery wall with resultant occlusion of the lumen, which commonly affects the left anterior descending artery, is a consistent gross finding. An inflammatory infiltrate, which is predominantly composed of eosinophils in the tunica adventitia and tunica media and is often accompanied by a hematoma in between these 2 layers, is observed histologically. The etiology remains unclear, but an increase in the activity of eosinophils because of hormonal interactions during pregnancy has been suggested. Interplay of hormones is thought to culminate in the release of histolytic agents by the eosinophils, which initiate the dissection process. Currently, there is no specific treatment for eosinophilic coronary monoarteritis, but cyclophosphamide and prednisone have shown positive results in the treatment of spontaneous coronary artery dissection with unspecified periadventitial inflammation. Percutaneous coronary procedures have also resulted in favorable outcomes in a subset of patients. Because of the high, sudden death rate in eosinophilic coronary monoarteritis, deciphering the underlying pathophysiology of this almost invariably fatal disease remains both a challenge and a key to developing screening methods that will allow timely detection and thus treatment.