Cardiovascular and infectious diseases remain the most common causes of death among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Basic science and epidemiological studies indicate that vitamin D has importance not only for cardiovascular health, but also for the immune response. Vitamin D signaling pathways regulate both innate and adaptive immunity, maintaining the associated inflammatory response within physiological limits. Levels of both the inactive as well as active form of vitamin D (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, respectively) are decreased in patients with CKD and ESRD. It is reasonable to hypothesize, therefore, that the immune dysfunction associated with vitamin D deficiency in patients with CKD and ESRD in part explains the misdirected inflammatory response and increased susceptibility to infection seen in this population. Indeed, observational studies show that vitamin D deficiency in patients with ESRD is associated with increased mortality, and treatment with vitamin D is associated with a decreased risk of infection, as well as reduced all-cause mortality. However, whether different vitamin D preparations have differential effects on physiological function and clinical outcomes is still unclear. A proper understanding of the immune regulatory function of vitamin D is important for the development of future therapeutic strategies.