Low vitamin D status, which is endemic due to inadequate oral intake combined with sun avoidance, contributes to musculoskeletal and other pathologies. Although controversial, it is increasingly recommended that serum 25-hydroxyvitamin D (25D) concentrations less than 30 ng/mL be considered suboptimal. Clinicians should appreciate that 25(OH)D measurements, like all quantitative laboratory tests, are subject to assay and biologic variability. Additionally, international standardized calibrators do not exist for 25(OH)D measurement. As such, a single 25(OH)D value of "30 ng/mL" may have substantial variability surrounding it, thereby making 25(OH)D levels of approximately 35 to 40 ng/mL a reasonable therapeutic goal to assure vitamin D adequacy. Achieving such levels often requires vitamin D supplementation. Vitamin D3 (cholecalciferol) or D2 (ergocalciferol) may be used; whether vitamin D3 is more potent than vitamin D2 in maintaining 25(OH)D is controversial.