Tumor lysis syndrome (TLS) is a complication of malignancies with high tumor cell proliferation, tumor burden, and chemosensitivity. It manifests with the release of intracellular components and results in hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia. These biochemical abnormalities may lead to serious complications such as renal failure, cardiac dysrhythmias, and death. Rasburicase, a recombinant urate oxidase enzyme, is a new agent indicated in the treatment or prophylaxis of hyperuricemia in pediatric patients with cancer who are at high risk for TLS. We reviewed the evidence for treatment with this agent compared with standard therapy with allopurinol. Rasburicase may be considered for use in patients with hyperuricemia at presentation and in patients at high risk for TLS that would otherwise result in a delay in chemotherapy. However, randomized controlled trials are required to establish the comparative efficacy of rasburicase in the adult population. Preliminary evidence suggests that single-dose or reduced-dose rasburicase may be effective in the prophylaxis and the treatment of hyperuricemia and TLS. However, to our knowledge, there is no evidence comparing clinically relevant outcomes such as acute renal failure or dialysis.