The opening chapter of this book, by scientist Dr. Robert Furchgott, details the discovery of endothelium’s role in the vasodilator effect of acetycholine in 1978. Its subsequent identification as nitric oxide has been critical to cardiovascular medicine in understanding the regulation of vascular homeostasis. This simple observation won Dr. Furchgott a Nobel Prize in 1998. Spanning from these initial observations to recent clinical investigations, this work offers an invaluable historical reference and clinical explanation about the intracellular mechanisms that regulate and stimulate endothelial nitric oxide synthase (eNOS). The basic mechanisms leading to endothelial dysfunction in cardiovascular disease complement information about the biological role and regulation of endothelial nitric oxide. Clinical studies of impaired endothelial function in patients with different cardiovascular conditions also reveal important and effective therapeutic strategies. Written for both established physicians and scientists investigating the basic mechanisms and treatment of cardiovascular disease, as well as medical students who want to initiate themselves in the study of endothelial regulation of vascular physiology, many will find this comprehensive review a stimulus for new research.