Methotrexate is a useful antimetabolite for the treatment of both benign and malignant proliferative disorders. When the pharmacokinetics and potential toxicity of this drug are understood, treatment regimens can be tailored to the underlying kinetics of the target population. With the appropriate knowledge of the importance of urinary excretion of methotrexate and factors that influence this and with the ready availability of leucovorin, toxicity can be avoided in all but the most unusual of circumstances.