Severe hypophosphatemia can cause generalized muscle weakness, paralysis of the respiratory muscles, myocardial dysfunction, reduced peripheral vascular resistance, and encephalopathy. Here we conducted a prospective study to determine the incidence of hypophosphatemia in 47 children on continuous renal replacement therapy and to evaluate the efficacy and safety of adding phosphate to the replacement and dialysate solutions of 38 pediatric patients. During continuous renal replacement therapy, 68% of patients were found to have hypophosphatemia, significantly more than the 12% of patients at the beginning of therapy. There was no higher incidence of hypophosphatemia among patients requiring insulin, diuretics, parenteral nutrition, or high doses of vasoactive drugs. In the children to whom phosphate was not added to replacement and dialysate solutions, 85% presented with an incidence of hypophosphatemia and 36% required intravenous phosphate replacement, rates significantly higher than in those patients where phosphate was added to the solutions. Phosphate supplementation did not cause any instability of the mixtures or other complications. We show here that the incidence of hypophosphatemia in children on continuous renal replacement therapy is very high. Further, we show that the addition of phosphate to replacement and dialysate solutions is safe and that it reduces the incidence of hypophosphatemia and the need for intravenous phosphate treatment.