Tumor lysis syndrome is an oncologic emergency that is characterized by severe electrolyte abnormalities and, frequently, by acute renal failure. The syndrome typically occurs in patients with lymphoproliferative malignancies, most often after initiation of treatment. The pathophysiology involves massive tumor cell lysis resulting in the release of large amounts of potassium, phosphate, and uric acid. Deposition of uric acid and calcium phosphate crystals in the renal tubules may lead to acute renal failure, which is often exacerbated by concomitant intravascular volume depletion. The kidney normally excretes these products, and consequently preexisting renal failure exacerbates the metabolic derangements of tumor lysis syndrome. Standard treatment aims to clear high plasma levels of potassium, uric acid, and phosphorus; correct acidosis; and prevent acute renal failure by way of aggressive intravenous hydration; lowering serum potassium levels; use of allopurinol; urinary alkalinization; or renal replacement therapy (if necessary). Allopurinol is the standard of care for treating hyperuricemia of malignancy, but is associated with drawbacks. Recombinant urate oxidase (rasburicase), which recently became available in the United States, provides a safe and effective alternative to allopurinol for lowering uric acid levels and preventing uric acid nephropathy.