Methotrexate is a potent antimetabolite and antifolate drug widely used in the treatment of various cancers, autoimmune disorders, and ectopic pregnancies. It works by inhibiting the enzyme dihydrofolate reductase (DHFR), thereby interfering with DNA synthesis, repair, and cell replication, particularly in rapidly dividing cells. Developed in the late 1940s and early 1950s, methotrexate was first introduced as a chemotherapeutic agent for childhood leukemia, marking a significant milestone in cancer treatment. Over time, its therapeutic applications expanded to include rheumatoid arthritis, psoriasis, and other autoimmune conditions due to its immunosuppressive properties. Today, methotrexate remains a cornerstone in oncology and rheumatology, valued for its efficacy, versatility, and well-established role in both cancer chemotherapy and immune modulation.