The pathogenesis of cardiovascular disease involves a complex and multifactorial process. Accumulating evidence indicates that inflammation and endothelial dysfunction may play a fundamental role in the initiation, progression and ultimately in the clinical manifestation of progressive vascular diseases. The vasodilator, anti-inflammatory and antithrombotic properties of the endothelium are dynamically regulated and are severely compromised by a variety of injuries, including atherosclerosis and inflammation. Endothelial dysfunction can occur well before the structural manifestation of atherosclerosis. It is therefore of great importance to develop non-invasive means of evaluating a broader array of endothelial function in vivo, to identify arteries at risk for atherothrombosis and its consequences, and to predict prognosis in patients with vascular disease. Recent studies identified novel biomarkers of vascular disease that would serve as indicators of widespread vascular inflammation or as surrogates for endothelial dysfunction. This review will focus on Creactive protein, serum amyloid A protein, myeloperoxidase, the cytokines interleukin-8 and interleukin-18, the CD40/CD40 ligand system, platelet-activating factor acetylhydrolase, lectin-like oxidized low-density lipoprotein receptor- 1 and gelatinolytic matrix metalloproteinases. Identifying biomarkers with sensitivity and specificity for detection of inflammation underlying endothelial dysfunction will increase our understanding of disease mechanisms, may allow early and more accurate prediction and diagnosis of disease progression, and ultimately may guide the development of novel therapeutic approaches directed towards prevention of vascular disease progression.