Vitamin D insufficiency and deficiency have been identified as having a correlation with poor clinical outcomes in patients with chronic kidney disease (CKD). The availability of vitamin D for metabolism into 25(OH)D and the ability to further metabolize to 1,25(OH)D are known to have a significant impact on the endocrine system and the modulation of iPTH, calcium, and phosphorus imbalances in patients with CKD. Until recently, the focus of care for these patients has been to support the endocrine need for 1,25(OH)D because the loss of kidney function eliminates the ability to synthesize calcitriol effectively. However, recent findings have identified an autocrine role for vitamin D and its metabolism at local sites as having a potentially profound impact on gene transcription and clinical outcomes in multiple body systems. The National Kidney Foundation Kidney Disease Outcomes Quality Improvement guidelines recommend the use of ergocalciferol in the treatment of vitamin D insufficiency in CKD Stages 3 and 4, and the use of active vitamin D hormone in the treatment of vitamin D deficiency in patients with CKD Stage 5 who also have secondary hyperparathyroidism. Data clearly identify that the insufficiency of 25(OH)D persists as patients progress through Stage 3 and Stage 4 CKD into Stage 5 CKD. This article discusses the treatment of both the deficiency and insufficiency by supplementing both the endocrine and autocrine pathways with appropriate vitamin D therapies.