Methotrexate is well established in the drug treatment of various neoplastic diseases. More recently it has become increasingly used as a once-weekly, low-dose treatment of disorders such as psoriasis and rheumatoid arthritis. Clinical trials have shown its effectiveness in these conditions and it is likely that dentists will encounter patients taking this drug in general dental practice. Oral ulceration can occur as a side effect of methotrexate therapy. This may be due to lack of folic acid supplementation or overdosage due to confusion regarding its once-weekly regime. Illustrations of these problems, which have initially presented in a dental setting, are given. Important drug interactions of methotrexate relevant to dentistry are discussed.