Methotrexate (MTX) is an important component of therapy in several immune diseases (rheumatoid arthritis, psoriasis, and cancers such as acute lymphoblastic leukaemia, osteosarcoma, ovarian cancer and others). Despite its clinical success, treatment with MTX often causes toxicity, dose reduction or treatment cessation. In this book, the authors present topical research in the study of the pharmacology, clinical uses and adverse effects of methotrexate. Topics discussed include lipid alterations instigated by methotrexate; acute toxicity of high doses of methotrexate in the treatment of lymphoblastic leukaemia in children; pharmacogenetics update on MTHFR and methotrexate toxicity; animal models of cognitive impairment induced by methotrexate and damage, as well as the recovery of the bone and bone marrow following methotrexate chemotherapy.