Background. The Youden index, the sum of sensitivity and specificity minus one, is an index used for setting optimal thresholds on medical tests. Discussion. When using this index, one implicitly uses decision theory with a ratio of misclassification costs which is equal to one minus the prevalence proportion of the disease. It is doubtful whether this cost ratio truly represents the decision maker's preferences. Moreover, in populations with a different prevalence, a selected threshold is optimal with reference to a different cost ratio. Summary. The Youden index is not a truly optimal decision rule for setting thresholds because its cost ratio varies with prevalence. Researchers should look into their cost ratio and employ it in a decision theoretic framework to obtain genuinely optimal thresholds. © 2010 Smits; licensee BioMed Central Ltd.