Control of serum phosphorus (P) levels is a central goal of managing patients with chronic renal failure (CRF). Hyperphosphatemia develops invariably with kidney failure, and inadequate control of serum P leads to an elevated calcium-phosphorus (Ca x P) product. Further contributing to an elevated Ca x P product is the fact that hemodialysis patients are generally in a net positive calcium balance-dietary intake of calcium, ingestion of calcium-based phosphate binders, calcium absorption from dialysate, and abnormalities in bone buffering and turnover all contribute to the calcium burden in hemodialysis patients. In addition, treatment with calcitriol to manage secondary hyperparathyroidism increases intestinal absorption of both calcium and P. These abnormalities in divalent ion metabolism can result in a number of harmful conditions in CRF patients, including vascular calcification, cardiovascular disease, calciphylaxis, and death. We are now beginning to realize that our current therapeutic approaches to CRF management may not only be ineffective in controlling P and Ca x P product, but may actually contribute to serious calcific and cardiovascular hazards in these patients. Elevated P and Ca x P product are both significant predictors of cardiovascular mortality in hemodialysis patients. These effects are observed at P and Ca x P product levels that were considered safe until recently. Based on current national studies, we now recommend that serum P levels and Ca x P product of patients with CRF be maintained between 3.0-5.0 mg/dl and less than 55 mg2/dl2, respectively. Achieving these more rigorous treatment goals will require a shift in our therapeutic management strategies to incorporate aggressive use of calcium-free phosphate binders and, when necessary, use of less calcemic vitamin D analogs.