The pathophysiology of hyperphosphatemia associated with end-stage renal disease and treatment with phosphate binders are discussed.Phosphorus is an essential element necessary for the normal function of the human body, required for skeletal construction and synthesis of DNA, proteins, and adenosine triphosphate. In healthy individuals, serum phosphorus concentrations are maintained between 2.5 and 4.5 mg/dL through diet and renal excretion. In renal insufficiency, phosphorus excretion declines and hyperphosphatemia develops. The body's compensation mechanisms cause secondary hyperparathyroidism and renal osteodystrophy. Phosphate binders provide an effective means for managing serum phosphate. Commercially available phosphate binders include calcium carbonate, calcium acetate, sevelamer, lanthanum, and, rarely, aluminum hydroxide. Because of aluminum's known toxicities, aluminum-based phosphate binders have a limited place in therapy. Calcium carbonate's benefits are seen over a narrow gastric pH range, thereby limiting the drug's utility. Calcium acetate is effective over a wide pH range. Other phosphate binders, including sevelamer hydrochloride and lanthanum carbonate, have recently entered the market, but their use remains controversial.If left untreated, hyperphosphatemia can result in secondary hyperparathyroidism, renal osteodystrophy, and metastatic calcification of blood vessels and soft tissue. The treatment of hyperphosphatemia in patients with chronic renal failure includes dialysis, dietary phosphorus restrictions, phosphate-binding medications, and vitamin D analogs. Selection of phosphate binders should be based on patient characteristics, including serum phosphate, serum calcium, and intact parathyroid hormone concentrations, and patient tolerability.