Diabetes has a profound impact on the cardiovascular system, and oxidative stress is likely an important mechanism through which diabetes adversely affects that system. Numerous animal and some human studies support the role of oxidative stress as a unifying hypothesis linking hyperglycemia to distinct cardiovascular pathophysiologic processes. The ultimate mechanism of excess production of ROS in diabetes likely involves multiple enzymatic sources of ROS that are both convergent upon common cellular and molecular targets and interrelated with positive feedback loops occurring between these different enzymatic systems. Particular roles of mitochondrial electron transport chain, Nox family NADPH oxidases, and uncoupled NO synthase(s) have been documented. While the experimental data linking oxidative stress to the cardiovascular complications of diabetes are quite extensive, as is the case in many other settings, there is a lack of convincing data in humans demonstrating a protective effect of antioxidants on diabetic cardiovascular disease. Nonetheless, strategies to reduce disrupted redox cell signaling and oxidative stress may find applicability regarding the treatment and prevention of the cardiovascular complications of diabetes.