Tumor lysis syndrome (TLS) refers to the constellation of deranged metabolic state, characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and/or azotemia, secondary to rapid breakdown of tumor cells. It is a life threatening emergency that typically follows administration of chemotherapy or may be spontaneous. Malignancies which have a large tumor burden, rapid turnover, as well as speedy breakdown following chemotherapy are susceptible. Acute lymphoblastic leukemia and non-Hodgkins lymphoma (particularly Burkitt's lymphoma) are typically predisposed. TLS is best managed by early anticipation and preventive measures than the complicated task of treating an established TLS. Vigorous intravenous hydration is the cornerstone of prevention as well as treatment. Rasburicase has revolutionized the management. It is available in India for past 1 1/2 y, although the cost is a limiting factor. Children with acute leukemia in developing countries may reach health facility late, with severe anemia and hyperleukocytosis. Exchange transfusion may have to be restored to in such patients to simultaneously correct anemia and hyperleukocytosis and enable safe administration of fluids. Dialysis may be required when the metabolic 'trash' overwhelms the renal excretion, resulting in renal failure. Chemotherapeutic drugs are often administered in a phased manner in susceptible patients, in an attempt to prevent precipitous lysis of tumor cells. Presentation and management of TLS in relevance to the pediatric emergency room is outlined.