Both the macro- and microvascular complications adversely affect the life quality of patients with diabetes and have been the leading cause of mortality and morbidity in this population. With the advancement of technologies in biomedical research, we have gained a great deal of understanding of the mechanisms underlying these complications. While euglycemic control still remains the best strategy, it is often difficult to maintain at a level that can completely prevent the vascular complications. Therefore, it is necessary to use the processes leading to vascular dysfunction as a framework for designing novel molecular therapeutic targets. Several of the mechanisms by which diabetes induces vascular complications include increased flux through the polyol pathway, increased oxidative stress, activation of protein kinase C (PKC), vascular inflammation, and abnormal expression and actions of cytokines in the vasculature. Many of the therapies that target these pathways have proven successful in experimental models of diabetic complications. However, clinical studies using these treatments have mainly yielded inconclusive results. The pathogenesis of diabetic vascular complications and results from animal studies and key clinical studies are reviewed here.