We have some concerns about the recommendations on cholinesterase inhibitors in the recent guidelines on mild cognitive impairment (MCI).1 Evidence in the guidelines, and in systematic reviews,2–4 clearly shows that cholinesterase inhibitors have no reliable benefit on cognition and do not reduce progression to dementia. At the same time, patients are exposed to risk: “side effects… are common, including gastrointestinal symptoms and cardiac concerns.”1 It is, therefore, curious that the message to practitioners is equivocal. They “may choose” not to use these medicines (recommendation B3a), or choose to actively prescribe them after “first discuss[ing] with the patient the fact this is…not currently backed by empirical evidence” (recommendation B3b).1 This is the first instance we recall of a learned academy legitimizing prescription of a class of drugs recognized to be ineffective. Given the guidelines’ potential for influence, we are deeply concerned that patients—who often are ill-equipped to make judgments of this kind—may be unnecessarily exposed to harm, and health care systems to needless cost. More generally, we are anxious to avoid a precedent for evidence being viewed as “optional” in clinical decision-making. We call upon the American Academy of Neurology and authors to retract recommendation B3b and rewrite B3a to plainly recommend against use of cholinesterase inhibitors in MCI.