Evidence-based guidelines are considered an essential tool in assisting physicians, policymakers and patients when choosing among alternative care options and are considered unbiased standards of care. Unfortunately, depending on how their reliability is measured, up to 50% of guidelines can be considered untrustworthy. This carries serious consequences for patients' safety, resource use and health economics burden. Although conflict of interests, panel composition and methodological flaws are traditionally thought to be the main reasons undermining their untrustworthiness, corruption and waste of biomedical research also contribute. We discuss these issues in the hope for a wider awareness of the limits of guidelines.