Methotrexate (MTX), a folate antagonist, is a crucial drug in the treatment of childhood ALL, both in the consolidation phase as high dose MTX (HDMTX) and in the maintenance phase as well as in the weekly low dose administration acting via competitive inhibition of DHFR, the reducer of dihydrofolate (DHF) into tetrahydrofolate (THF). The gene discussed is DHFR; the disease is acute lymphoblastic leukemia.