The vitamin D endocrine system is central to the control of bone and calcium homeostasis. Thus, alterations in the vitamin D pathway lead to disturbances in mineral metabolism. Furthermore, a role for vitamin D has been suggested in other diseases, like cancer, diabetes and cardiovascular disease. Expression and nuclear activation of the vitamin D receptor (VDR) are necessary for the effects of vitamin D. Several genetic variations have been identified in the VDR. DNA sequence variations, which occur frequently in the population, are referred to as "polymorphisms" and can have biological effects. To test whether there is a linkage between VDR polymorphisms and diseases, epidemiological studies are performed. In these studies, the presence of a variation of the gene is studied in a population of patients, and then compared to a control group. Thus, association studies are performed, and a link among gene polymorphisms and diseases can be established. Since the discovery of VDR polymorphisms a number of papers have been published studying its role in bone biology, renal diseases, diabetes, etc. The purpose of this review is to summarize the vast amount of information regarding vitamin D receptor polymorphisms and human diseases, and discuss its possible role as diagnostic tools.