Folates are involved in a variety of important biosynthesis by way of donating one carbon unit. Since folate metabolism was well understood a number of antifol have been developed. Among these antifols, aminopterin was first used in the treatment of childhood leukemia. However due to its toxicity and purity problems. it was immediately replaced by another antifols. methotrexate (MTX). MTX is shown to be active against various malignancies including leukemia breast cancer, osteogenic sarcoma, and head and neck cancer. Clinically, MTX therapy is divided into 3 categories. depeding on the dose administered; low-dose is defined as doses < $80;mg/m^2$ intermediate-dose as doses $geqq;80;mg/m^2$ and < $1000;mg/m^2$ and high-dose as doses $geqq;1000;mg/m^2$. Leucovorin should be administered to minimize MTX toxicities when MTX doses are greater than $80-100;mg/m^2$. The clinical pharmacokinetics (ADME) of MTX is discussed in this text.