The vascular endothelium contributes to and is affected by inflammatory processes. Disturbance of the endothelium's morphologic and functional integrity in response to mechanical, immunologic, and chemical injuries reflects the first step in the pathophysiological cascade of atherosclerotic disorders. At the site of an endothelial injury, invading inflammatory cells producing numerous proinflammatory factors promote and amplify both local and systemic inflammation. These early changes on a cellular and subcellular level that precede the clinical manifestation of atherosclerosis are associated with loss of profound physiological functions of the endothelium. One pivotal function of the endothelium is nitric oxide-mediated regulation of vessel tone and blood flow according to the local requirements. The assessment of nitric oxide-mediated endothelial function by different methods revealed a close relation between inflammatory activation and endothelial dysfunction in healthy volunteers, patients at risk, and patients with established cardiovascular disease. Moreover, anti-inflammatory therapeutic interventions do not only have a positive impact on disease progression, but also on endothelial function, thus further providing an indirect line of evidence linking inflammation with endothelial dysfunction.