Acute tumor lysis syndrome (TLS) is characterized by the triad of hyperuricemia, hyperkalemia, and hyperphosphatemia and is caused by the death of tumor cells and release of intracellular contents into the circulation. This syndrome is most frequently associated with hematopoietic malignancies with a high growth fraction, including acute leukemias and lymphomas, but can be encountered in patients with nonhematopoietic solid tumors. Acute tumor lysis is typically precipitated by chemotherapy leading to rapid cell death, but may also occur spontaneously prior to treatment. In severe cases, the metabolic abnormalities of TLS can cause renal failure, cardiac arrhythmias, and death. Standard therapies include intravenous hydration, alkalinization of the urine to increase the solubility of uric acid, and administration of allopurinol to block production of uric acid. Recombinant urate oxidase (rasburicase) is a newer agent that directly cleaves uric acid. It is important for the clinician to maintain a high level of clinical suspicion for TLS when initiating therapy in children newly diagnosed with cancer, including those with solid tumors, and to know how to prevent and treat this potentially deadly metabolic complication.