Recent decades have witnessed the revelation of expanding roles of the vitamin D endocrine system beyond calcium and phosphorus metabolism. Along with these non-calcemic or non-classic actions of vitamin D are newly discovered therapeutic actions of vitamin D analogs in a number of pathological conditions, including kidney disease. The kidney is the major organ involved in the synthesis of the hormonal metabolite of vitamin D, and vitamin D deficiency is a common feature of chronic kidney disease even in its early stages. Experimental data suggest that vitamin D deficiency may in turn accelerate the progression of kidney disease. Low-calcemic vitamin D analogs have exhibited impressive therapeutic effects in various kidney disease models, with targets ranging from the NF-kappaB pathway to the renin-angiotensin system. These recent studies demonstrate that vitamin D analogs have potent renoprotective effects. The emerging experimental and clinical evidence has provided a solid foundation for the continuing exploration of vitamin D analogs in prevention and intervention in kidney disease.