Current evidence regarding the clinical consequences of hypophosphatemia is not straightforward. Given the potentially different implications of hypophosphatemia among various patient groups, this commentary touches on patients with low serum phosphate after acute hospitalization, those with chronic ambulatory hypophosphatemia, and those with hypophosphatemia in the setting of advanced renal disease. Finally, this commentary examines the evidence regarding how best to replete phosphorous in the hypophosphatemic patient.