Vitamin D receptor agonists (VDRA) are currently recommended for the treatment of secondary hyperparathyroidism in stage 5 CKD. They are considered to be contraindicated in the presence of low or normal (for a dialysis patient) levels of PTH due to the risk of developing adynamic bone disease, with consequent vascular calcification. However, these recommendations are increasingly at odds with the epidemiological evidence, which consistently shows a large survival advantage for patients treated with low-dose VDRAs, regardless of plasma calcium, phosphate, or PTH. A large number of pleiotropic effects of vitamin D have been described, including inhibition of renin activity, anti-inflammation, and suppression of vascular calcification stimulators and stimulation of vascular calcification inhibitors present in the uremic milieu. Laboratory studies suggest that a normal cellular vitamin D level is necessary for normal cardiomyocyte and vascular smooth muscle function. While pharmacological doses of VDRA can be harmful, the present evidence suggests that the level of 1,25-dihydroxycholecalciferol should also be more physiological in stage 5 CKD, and that widespread use of low-dose VDRA would be beneficial. A randomized controlled trial to test this hypothesis is warranted.