Serum 25-hydroxyvitamin D3 [25(OH)D3] concentrations are currently recognized as the functional status indicator for vitamin D. Evidence is reviewed that shows that serum 25(OH)D3 concentrations of < 80 nmol/L are associated with reduced calcium absorption, osteoporosis, and increased fracture risk. For typical older individuals, supplemental oral intakes of approximately 1300 IU/d are required to reach the lower end of the optimal range. Evidence of substantial problems in routine clinical measurement of serum 25(OH)D3 concentrations among patients is cited. There is great need for standardization and improved reproducibility and sensitivity of measurements of serum 25(OH)D3 concentrations.