Methotrexate has a place in the treatment of an increasing number of diseases. Its emerging role in the treatment of primary biliary cirrhosis and inflammatory bowel disease still requires further evaluation. Its toxicity profile is wide and is affected by a variety of factors. Hepatotoxicity from long-term use in patients with psoriasis and rheumatoid arthritis holds particular concern for the physician. Appropriate monitoring guidelines for hepatotoxicity can only be made after careful evaluation of available data and consideration of cost-to-benefit models.