The renin-angiotensin system (RAS) is a central regulator of renal and cardiovascular functions. Over-activation of the RAS leads to renal and cardiovascular disorders, such as hypertension and chronic kidney disease, the major risk factors for stroke, myocardial infarction, congestive heart failure, progressive atherosclerosis, and renal failure. Mounting epidemiological and clinical evidence has demonstrated an association of vitamin D deficiency or insufficiency with increased risks of renal and cardiovascular diseases. Long-term vitamin D deficiency can lead to over-activation of the RAS. Because of the broad involvement of the RAS in the development of renal and cardiovascular diseases, such findings have invaluable pathophysiological and therapeutic implications. They provide a mechanistic insight into the ever-increasing epidemiological and clinical evidence linking vitamin D deficiency to renal and cardiovascular problems in the general population. They also provide a molecular basis to explore the therapeutic potentials of vitamin D and its analogs in the prevention and intervention of these diseases. Therefore, the rising prevalence of hypertension and chronic kidney disease around the world attests the urgent need for new and more effective therapeutic methods.