Tumor lysis syndrome (TLS) is widely recognized as a serious adverse event associated with the cytotoxic therapies primarily used in hematologic cancers, such as Burkitt lymphoma and acute lymphoblastic leukemia. In recent years, TLS has been more widely observed, due at least in part to the availability of more effective cancer treatments. Moreover, TLS is seen with greater frequency in solid tumors, and particularly in bulky tumors with extensive metastases and tumors with organ or bone marrow involvement. The consequences of TLS include the serious morbidity and high risk of mortality associated with the condition itself. Additionally, TLS may delay or force an alteration in the patient’s chemotherapy regimen. The changing patterns of TLS, as well as its frequency, in the clinical setting, result in unnecessarily high rates of illness and/or fatality. Prophylactic measures are widely available for patients at risk of TLS, and are considered highly effective. The present article discusses the various manifestations of TLS, its risk factors and management options to prevent TLS from occurring.