With the growing worldwide obesity epidemic, obesity, type 2 diabetes mellitus and hypertension leading to premature cardiovascular events, are increasingly prevalent. Diabetes mellitus is a significant public health concern and more aggressive management of the condition and its complications, particularly cardiovascular disease, is warranted. Endothelial cell dysfunction is now known to be present at the earliest stages of metabolic syndrome, and insulin resistance and may precede the clinical diagnosis of type 2 diabetes mellitus by several years. The current focus on endothelial cell function as a potential target of pharmacotherapy in the management of cardiovascular disease in diabetics seems warranted, though not all drugs currently prescribed target endothelial cell function equally. In this review, we consider the six classes of drugs currently prescribed for the treatment of hypertension as they impact endothelial cell function and advocate for the development of novel drugs that can repair the endothelium and enhance nitric oxide availability thus preventing future cardiovascular events.