Hepatoxicity is a major adverse reaction that can occur during methotrexate treatment of the rheumatic diseases. The pathologic lesions are nonspecific and the pathogenesis is poorly understood. Early studies in psoriasis clearly established a relationship between hepatic injury and several risk factors, particularly alcohol use. Methotrexate hepatoxicity occurs less frequently in rheumatoid arthritis than previously reported in psoriasis patients. Consequently, the American College of Rheumatology guidelines for methotrexate monitoring do not recommend baseline and surveillance liver biopsies in low-risk patients. These guidelines seem to be useful and cost-effective.