Previous reviews have summarized how a reduced expression of the endothelial nitric oxide synthase (eNOS) enzyme and subsequent decreased production of NO result in an increased susceptibility/risk to develop essential hypertension [1,2], preeclampsia [3], diabetic nephropathy [4], retinopathy [5], migraine [6], and erectile dysfunction [7]; the role of the eNOS enzyme, including its modulation, regulation, and relevance within the cardiovascular system (CVS) in both normal physiological state and in several important cardiovascular diseases is elaborated. Here, NOS3 is linked to diabetic kidney disease.