To help account for and address observed variations in medical practice, evaluations of “appropriateness” have sought to supplement incomplete evidence with professional opinion. This article contributes to an understanding and refinement of the construct of appropriateness by discussing how it has been defined and applied in studies of health care in general and prescribing in particular. We suggest that appropriateness is the outcome of a process of decisiondashmaking that maximises net individual health gains within society's available resources. This definition distinguishes between (in)appropriate prescribing, as an outcome, and (ir)rational prescribing as a process. To assess appropriateness, we advocate combining explicit criteria with independent review in cases of uncertainty and disagreement. Refinements based on reviews using implicit criteria should draw on shared professional knowledge and post hoc state the process followed as explicitly as possible. The Medication Appropriateness Index is shown to provide a solid foundation for identifying dimensions of prescribing appropriateness.