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The role of vitamin D in maintaining bone health has been known for decades. Recently, however, the discovery that many tissues expressed the vitamin D receptor and were able to transform the 25-OH vitamin D into its most active metabolite, 1,25-(OH)2 vitamin D, has led to a very promising future for this “old” molecule. Indeed, observational studies, and more and more interventional studies, are raising the importance of a significant vitamin D supplementation for not-only skeletal benefits. Among them, 25-OH vitamin D has been found to play an important role in prevention of cancers, auto-immune diseases, cardiovascular diseases, diabetes, and infections. Vitamin D deficiency, defined as serum 25-OH vitamin D levels <30 ng/mL, is very common in our population. The cost/benefit ratio and some recently published studies are clearly now in favor of a controlled and efficient vitamin D supplementation in these patients presenting a 25-OH vitamin D level <30 ng/mL. More attention should also be focused on pregnant and lactating women, as well as children and adolescents.