The long-term efficacy of methotrexate has been proved in prospective trials. With the chronic administration of methotrexate, however, concern has been raised about its safety. While side effects are common, they are seldom life threatening and rarely necessitate withdrawal of the drug. Serious side effects of methotrexate include hepatic, hematologic, and pulmonary toxicity. These toxicities are much less common, but usually result in the withdrawal of the drug. With careful monitoring of patients symptoms and laboratory test, however, these toxicities can be minimized or even prevented.