Although approximately half of patients undergoing hemodialysis receive activated forms of Vitamin D, the primary reason to initiate this therapy has rested solely on the management of secondary hyperparathyroidism. Secondary hyperparathyroidism is likely one of several consequences of Vitamin D deficiency, and only now have other consequences of Vitamin D deficiency emerged. Although previously viewed as a contributor to hypercalcemia and hyperphosphatemia, recent studies suggest Vitamin D may improve cardiovascular structure and function, improve vascular compliance, and reduce pro-inflammatory cytokines, all of which may contribute to the improved survival observed in retrospective studies examining the outcome of patients treated with activated Vitamin D compared to those who were not. The current review examines two recent large-scale studies of hemodialysis patients: one that demonstrated a survival advantage of paricalcitol over calcitriol, and a second that demonstrated a significant survival advantage of any intravenous Vitamin D formulation versus none. In both studies, the findings were independent of mineral and parathyroid hormone levels, suggesting "non-traditional" actions of Vitamin D contributed to the observed survival advantage. Potential steps moving forward in light of these observational studies are subsequently discussed.