Nephrologists are well aware of the therapeutic effects of activated vitamin D in managing secondary hyperparathyroidism. Beyond bone and mineral metabolism, however, we are now beginning to appreciate the effects of activating the vitamin D receptor (VDR) in other cell types. Our group and others recently found a survival advantage associated with injectable vitamin D therapy in hemodialysis populations. The observational nature of these studies, however, subjects them to the possibility that confounding and bias may have accounted for their results. Therefore, it is unclear if indeed a survival benefit exists, if harm is incurred with this therapy or if activation of the VDR in cell types other than bone, intestine, and the parathyroid gland are applicable to our patients with kidney disease. The range of studies being planned include those targeting the cardiovascular effects of VDR activation, further understanding of the prevalence and consequences of vitamin D deficiency in patients with kidney disease, trials to examine the effects of VDR activation on intermediate cardiovascular and noncardiovascular endpoints, and trials targeting mortality endpoints. If consistent with the recent observations, these studies may provide nephrologists with an intervention to alter the otherwise poor outcomes in patients with kidney disease.