The development of our understanding of the function of vitamin D from its discovery in the second and third decades of the 20th century to its hormonal activation of its nuclear receptor and to its present position of an important factor in public health has been traced. The key discoveries of the conversion of vitamin D to its hormonal form, its regulation, and the evolving picture of its molecular mechanism of action are presented. The recognition of its role beyond mineralization of the skeleton to its role in skin, the immune system, and its protective role in some forms of malignancy represent more recent developments. The evolution of derivatives of 1α,25-dihydroxyvitamin D3 as therapeutic agents suggests a richness of therapeutic potential. All of this nevertheless illustrates that much more remains to be discovered and applied to our armaments for preventing and treating disease.