With the extensive development of imaging examination and functional assessment of coronary artery disease, the understanding of the pathogenesis of acute coronary syndrome (ACS) is constantly changing. Early opinions suggested that the causes of ACS were mainly severe coronary stenosis and complete obstructive coronary artery disease. However, in recent years, non-obstructive coronary artery disease, that is coronary angiography-confirmed ACS cases with culprit vessel stenosis ＜50%, has been increasingly recognized, which has also shown a significant gender difference. The pathogenesis of female patients with non-obstructive ACS are special, no longer limited to traditional risk factors for atherosclerosis. Pregnancy, the change of estrogen levels, hysterectomy, the use of a new generation of oral contraceptives, mental, and psychological factors could also play important roles in the pathogenesis of female non-obstructive ACS. Pathological manifestations are comprised of plaque rupture, and more frequently of plaque erosion, spontaneous coronary artery dissection, vasospasm, microvascular disease, and stress cardiomyopathy. Understanding the pathological mechanism and clinical features of female non-obstructive ACS is helpful to improve the clinical understanding and diagnosis of this disease, so as to develop the effective treatment.