The term vitamin D is linked to the development of rickets and osteomalacia, and has been known about since at least the 17th century. Prevention of these diseases has challenged many researchers in the following centuries, which has resulted in important advances in prevention and treatment. However, it was only in 1900 that the vitamin structure was identified. In the following decades, many steps were made toward understanding the metabolism of the vitamin. Recent progress has revolutionized our view of vitamin D and suggested that it has much wider effects on the body than ever believed. In addition to its well-known effects on calcium-phosphate homeostasis, vitamin D, through its hormonal form calcitriol, has been found to be a cell-differentiating factor and antiproliferative agent with actions on a variety of tissues. By influencing gene expression, calcitriol affects many physiological processes, besides calcium-phosphate homeostasis, including muscle and keratinocyte differentiation, blood pressure regulation and the immune response. The widespread expression of 1a-hydroxylating enzyme in peripheral tissues supports the view that it exists to boost intracellular concentrations of calcitriol within some target tissues in order to modulate a unique set of genes. This new information has profound implications for chronic kidney disease (CKD) patients with their tendency to vitamin D substrate insufficiency, coupled with their documented loss of the renal 1a-hydroxylase. Administration of vitamin D receptor activators such as calcitriol have been found to favor the survival of CKD patients mainly improving the cardiovascular system. In recent years, analogs of calcitriol such as paricalcitol, able to activate the vitamin D receptor, have shown additional biologic effects and advantages compared with calcitriol in the treatment of patients with chronic renal failure.