Wide discrepancies exist in the use of vitamins in kidney disease, and evidence-based recommendations are sparse. Water-soluble vitamin levels may be inadequate in patients not receiving supplements and this may be associated with increased mortality, which deserves further attention to increase strength of evidence. Supplements should be administered cautiously as renal mechanisms to prevent hypervitaminosis are no longer functional. The most reliable assays for vitamin status examine tissue mechanisms that rely on vitamins as cofactors. Vitamin A levels are generally quite high, vitamin D is low and requires supplementation, and the benefits of vitamin E may be linked to its usage in a modified dialysis membrane. Because of restricted diets that provide limited vitamin intake from food, many renal patients can benefit from a tablet that adds an amount equal to one recommended daily allowance of water-soluble vitamins, but larger amounts are not appropriate or beneficial. Vitamin status is influenced by interaction of many variables, and individual attention to each patient is warranted to achieve optimal vitamin status.