Vignette-based methodologies are frequently used to examine judgments and decision-making processes, including clinical judgments made by health professionals. Concerns are sometimes raised that vignettes do not accurately reflect “real world” phenomena, and that this affects the validity of results and conclusions of these studies. This article provides an overview of the defining features, design variations, strengths, and weaknesses of vignette studies as a way of examining how health professionals form clinical judgments (e.g., assigning diagnoses, selecting treatments). As a “hybrid” of traditional survey and experimental methods, vignette studies can offer aspects of both the high internal validity of experiments and the high external validity of survey research in order to disentangle multiple predictors of clinician behavior. When vignette studies are well designed to test specific questions about judgments and decision-making, they can be highly generalizable to “real life” behavior, while overcoming the ethical, practical, and scientific limitations associated with alternative methods (e.g., observation, self-report, standardized patients, archival analysis). We conclude with methodological recommendations and a description of how vignette methodologies are being used to investigate clinicians’ diagnostic decisions in case-controlled field studies for the ICD-11 classification of mental and behavioural disorders, and how these studies illustrate the preceding concepts and recommendations