question: Methotrexate (MTX) has long been considered a cornerstone drug for the treatment of rheumatoid arthritis (RA). As has been speculated previously, it may be the best-studied drug ever approved in rheumatic disease with many thousands of publications describing both its clinical effectiveness and many toxicity challenges (1). Much of what we learned about the drug was thankfully and conveniently inherited from superb oncology investigators (2). Rheumatologists have had a rich literature to draw upon to inform the manner in which the drug is used and monitored and thus readily prescribe MTX with ease. However, because of its ubiquitous prescribing and central position in RA therapeutics (3) its common use may confer a false sense of security. Indeed, there are many potential toxicities (1).