Methotrexate is a common drug with a long history; for the past 40 years, it’s been used to treat a range of diseases. Today it is the most commonly used drug for systemic rheumatic diseases worldwide and is the first drug a physician will prescribe for a patient with rheumatoid arthritis. But despite its use by millions of people, there is not robust data on the rates of the side effects of the drug. Observational studies have suggested that methotrexate may elevate a person’s risk of a variety of adverse events, including liver toxicity, anemia and difficulty in breathing, but the magnitude of risk was unknown. Taking advantage of data from the Cardiovascular Inflammation Reduction Trial (CIRT), a randomized double-blind, placebo-controlled trial, investigators from Brigham and Women’s Hospital have been able to far more accurately determine rates of adverse events for people taking methotrexate, finding small-to-moderate elevations in risks for skin cancer, gastrointestinal, infectious, lung, and blood adverse events. Results are published in Annals of Internal Medicine.