Abstract: Nitric oxide (NO), a key signaling molecule, plays an important role in physiological activities including blood pressure regulation, vascular tone maintenance and immune system regulation. In the cardiovascular system, abnormal productivity of NO is the incentive for many cardiovascular diseases. As a rate-limiting enzyme of NO, endothelial nitric oxide synthase (eNOS) is important in the regulation of blood vessel walls. Therefore, eNOS is closely related to normal cardiovascular functions. In this article we briefly describe the basic structure and functions of eNOS as well as the physico-chemical properties of NO. We then focused on the relationship between eNOS/NO signaling pathway and cardiovascular diseases such as endothelial dysfunction-related diseases, vascular remodeling, and ischemic cardiovascular diseases.