Tumor lysis syndrome (TLS) is a serious adverse event observed in patients treated for hematologic malignancies and solid tumors, particularly those with a high proliferative rate. An abrupt and massive tumor cell lysis with release their contents into the circulation leads to a rapid development of hyperuricemia, hyperkalemia, hyperphosphatemia, followed by hypocalcemia. If not managed appropriately, these metabolic disturbances may result in acute kidney injury and in life-threatening cardiac complications and even death. This short review summarizes current strategies for diagnosis, risk assessment, prophylaxis, and therapy.