Prevention is the most important factor in the management of TLS. Aggressive hydration prior to initiation of chemotherapy as well as during and after completion of the chemotherapy helps keep urine flowing and facilitates excretion of uric acid and phosphorus. In addition, for patients at moderate risk for developing TLS, eg, those with intermediate-grade lymphomas and acute leukemias, allopurinol should be given before starting chemotherapy at an oral dose of 100 mg/m2 every 8 hours (maximum 800 mg/day) with dose reductions for impaired kidney function. Rasburicase 0.1–0.2 mg/kg/day is given intravenously for 1–7 days to patients at high risk for developing TLS, eg, those with high-grade lymphomas or acute leukemias with markedly elevated white blood cell counts (acute myeloid leukemia, white blood cell count greater than 50,000/mcL [50,000/109/L] or acute lymphoblastic leukemia, white blood cell count greater than 100,000/mcL [100,000/109/L]). Rasburicase may be considered for patients with baseline elevated uric acid who are being treated with venetoclax (Bcl-2 inhibitor) for chronic lymphocytic leukemia who have large lymph nodes (10 cm or larger) or nodes 5 cm or larger accompanied by white blood cell counts greater than 25,000/mcL (25,000/109/L); or in any patient in whom hyperuricemia develops despite treatment with allopurinol. Rasburicase cannot be given to patients with known glucose 6-phosphate dehydrogenase (G6PD) deficiency nor can it be given to pregnant or lactating women. Systemic bicarbonate infusions to alkalinize the urine are not routinely recommended unless there is accompanying metabolic acidosis. In addition to the hyperuricemia, laboratory values should be monitored following initiation of chemotherapy; elevated potassium or phosphorus levels need to be promptly managed.