Compared to such native vitamin D agents as cholecalciferol (D3), egocalciferol (D2), and calcifediol (25- hydroxy vitamin D3, which need 1-alpha hydroxylase to be activated, 1-alpha-ergocalciferol, also known as doxercalciferol, is a synthetically manufactured vitamin D analog used for treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). Doxercalciferol exhibits more structural similarities to plant-based vitamin D2, ergocalciferol, than with animal-based vitamin D3, cholecalciferol. Because doxercalciferol does not have a 25-hydroxy group, it requires 25-hydroxylation by the liver to be activated, a process independent of kidneys. Doxercalciferol shares these features with its D3 equivalent, 1-alpha-hydroxy-cholecalciferol (alphacalcidol), both of which are activated hepatically and independent of renal or extra-renal 1-alpha hydroxylase. In experimental and clinical studies of CKD and SHPT, doxercalciferol effectively reduces parathyroid hormone levels and restores abnormal bone pathology. The efficacy of doxercalciferol is similar to other vitamin D analogs including calcitriol, alphacalcidol, paricalcitol (19-nor-1,25-dihydroxyvitamin D2 ) and maxacalcitol (1,25-dihydroxy-22-oxa-vitamin D3). The frequency and magnitude of hypercalcemia or hyperphosphatemia observed with doxercalciferol treatment may be less than calcitriol or alphacalcidol therapy but not less than such vitamin D-mimetics as paricalcitol or maxacalcitol. Doxercalciferol can be used for the treatment of SHPT across all ranges of CKD, particularly if hypercalcemia is of concern. There are limited data as to whether doxercalciferol confers greater efficacy or better outcome and survival than other vitamin D analogs and D-mimetics. Whereas further studies are warranted, doxercalciferol can safely be used for correction of SHPT in the entire spectrum of CKD.