Endothelial to mesenchymal transition (EndMT) is a special type of epithelial to mesenchymal transition. It is a process that is characterized by the loss of features of endothelial cells and acquisition of specific markers of mesenchymal cells. A variety of stimuli, such as inflammation, growth factors, and hypoxia, regulate EndMT through various signaling pathways and intracellular transcription factors. It has been demonstrated that epigenetic modifications are also involved in this process. Recent studies have identified the essential role of EndMT in the cardiovascular system. EndMT contributes to steps in cardiovascular development, such as cardiac valve formation and septation, as well as the pathogenesis of various cardiovascular disorders, such as congenital heart disease, myocardial fibrosis, myocardial infarction and pulmonary arterial hypertension. Thus, comprehensive understanding of the underlying mechanisms of EndMT will provide novel therapeutic strategies to overcome congenital heart disease due to abnormal development and other cardiovascular diseases. This review will focus on summarizing the currently understood signaling pathways and epigenetic modifications involved in the regulation of EndMT and the role of EndMT in pathophysiological conditions of the cardiovascular system.