This article explores how developers address uncertainty in the creation of an evidence-based guideline (EBG). As the aim of an EBG is to assist healthcare practitioners in situations of doubt, it is easy to assume that uncertainty has no place in guidelines. However, as we discovered, guideline development does not ignore uncertainty but seeks to accept it while establishing credible recommendations for healthcare. Dealing with omissions in knowledge, ignorance, or challenges in valuating different sorts of knowledge form the core of the work of guideline developers. Interviewing guideline developers, we found three types of valuation work: classifying studies, grading types of knowledge, and involving expertise and clinical practice. These methods have consequences for the credibility, and amount and kind of uncertainty EBGs can include.!