Accumulating evidence demonstrates that measures of vascular compliance correlate with endothelial function in animal models and patients with cardiovascular, metabolic, and kidney diseases. Nitric oxide modulates not only endothelial function, but also vascular compliance. Disruption of normal endothelial function may, at least partially, be responsible for reduced vascular compliance. Thus, nitric oxide may play a pivotal role as a mechanistic link between impaired vascular compliance and endothelial dysfunction.