Methotrexate (MTX) is a key drug in the chemotherapy for childhood acute lymphocytic leukemia (ALL). It is essential in the treatment of such areas as the central nervous system (CNS) and reproductive organs. High-dose chemotherapy is applied for this purpose to obtain an effective plasma concentration in the target organs. There are three major mechanisms of nephrotoxicity related with MTX. One is that induced by allergic reaction, which usually appears as interstitial nephritis. In this case MTX is contraindicated. Another is direct pharmacological toxicity against renal tubules. The third is precipitation of MTX, which plugs the renal tubules. The latter two are consequently dose dependent, and are usually associated with high-dose chemotherapy. To prevent these nephrotoxicities, hydration and alkalinization of the urine are performed to accelerate the urinary excretion and avoid the precipitation of MTX.