Endothelial dysfunction is an imbalance in the production of vasodilator factors and when this balance is disrupted, it predisposes the vasculature towards prothrombotic and pro-atherogenic effects. This results in vasoconstriction, leukocyte adherence, platelet activation, mitogenesis, pro-oxidation, impaired coagulation and nitric oxide production, vascular inflammation, atherosclerosis and thrombosis. Endothelial dysfunction is focussed as it is a potential contributor to the pathogenesis of vascular disease in diabetes mellitus. Under physiological conditions, there is a balanced release of endothelial-derived relaxing and contracting factors, but this delicate balance is altered in diabetes mellitus and atherosclerosis, thereby contributing to further progression of vascular and endorgan damage. This review focuses on endothelial dysfunction in atherosclerosis, insulin resistance, metabolic syndrome, oxidative stress associated with diabetes mellitus, markers and genetics that are implicated in endothelial dysfunction.