This chapter discusses the actions and deficiencies in action of calciferols. The calciferols are a group of compounds also known as the D vitamins; they are secosteroids, implying that they contain a steroidal configuration with one ring open. Vitamin D is generally considered to be an inactive precursor form with several properties appropriate for classification as a vitamin; 1,25(OH)2D is highly bioactive, adhering to the general model of action that characterizes the true steroidal hormones. The chapter also focuses on the activation and target interactions of calciferols. The initial step in the activation of circulating vitamin D is enzymatic conversion to 25(OH) vitamin D. The conversion of 25(OH)D to lα,25(OH)2D is the focal point in regulation of calciferol metabolism. This conversion occurs principally in the kidney, mediated by a mitochondria1 enzyme system of which one major component is a cytochrome P-450. The clinical, biochemical, radiological, and histological manifestations of calciferol deficiency represent the combined end result of the deficiency itself and compensatory mechanisms. The main function of active calciferol metabolites is maintenance of calcium and possibly phosphorus homeostasis.