Cardiovascular diseases (CVD) and infectious diseases represent the two most important causes of death in patients with chronic kidney disease (CKD). The traditional risk factors of CVD do not appear to account sufficiently for the increased risk of CVD in patients with CKD, and vitamin D deficiency appears to be an important non-traditional, and potentially modifiable, CVD risk factor in this patient population. 25-Hydroxyvitamin D (25(OH)D) is converted to its biologically active form, 1,25-dihydroxyvitamin D (1,25(OH)(2)D), by the enzyme 1α-hydroxylase in the kidneys. The recent discovery that many extrarenal tissues also possess both the 1α-hydroxylase enzyme and the vitamin D receptors has provided new insights into the important physiologic autocrine and paracrine roles of vitamin D in various tissues and organs that are mainly dependent on the availability of 25(OH)D from the circulating plasma. Accordingly, the present review focuses on the rapidly expanding body of clinical and experimental evidence that supports a strong association between 25(OH)D deficiency/insufficiency and the risk of adverse CVD outcomes and infectious diseases as well as on the non-calcemic autocrine and paracrine actions of vitamin D both in the general population and in patients with CKD.