Over the past century, industrialized societies have seen a meteoric rise in the so-called diseases of civilization: obesity, cardiovascular disease, osteoporosis, autoimmune disease and cancer. These disorders are often associated with apparent "deficiencies" in critical nutrients such as vitamins, minerals and hormones. This talk will examine the arguments for and against supplementation, together with the evidence from interventional studies. The focus will be on the supplementation with Vitamin C, Vitamin D, and calcium. I will argue that the case for supplementation as a long-term preventive strategy has not be made, and often overlooks the compensating effects of homeostatic regulation.