This chapter discusses the diagnosis, evaluation and management of tumor lysis syndrome (TLS). Risk for TLS can be stratified into high, intermediate, and low. The physical symptoms of TLS are usually related to an underlying electrolyte abnormality. The laboratory diagnosis of TLS is made by two or more of the derangements between 3 and 7 days after the onset of therapy for hematological malignancy. The derangements include hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. Acute kidney injury is usually related to hyperuricemia. Therapy is therefore aimed at reducing serum uric acid. Therapies that decrease serum uric acid level: allopurinol, rasburicase, and urinary alkalinization. Patients with TLS usually decompensate because of worsening electrolyte abnormalities. Interventions should target both the developing condition (cardiac arrhythmia, seizure, etc.) and the underlying electrolyte disorder.