CONTEXT With growing recognition that most forms of psychopathology are best represented as dimensions or spectra, a central question becomes how to implement dimensional diagnosis in a way that is empirically sound and clinically useful. Prototype matching, which involves comparing a patient's clinical presentation with a prototypical description of the disorder, is an approach to diagnosis that has gained increasing attention with forthcoming revisions to both the DSM and the International Classification of Diseases. OBJECTIVE To examine prototype diagnosis for mood and anxiety disorders. DESIGN, SETTING, AND PATIENTS In the first study, we examined clinicians' DSM-IV and prototype diagnoses with their ratings of the patients' adaptive functioning and patients' self-reported symptoms. In the second study, independent interviewers made prototype diagnoses following either a systematic clinical interview or a structured diagnostic interview. A third interviewer provided independent ratings of global adaptive functioning. Patients were recruited as outpatients (study 1; N = 84) and from primary care clinics (study 2; N = 143). MAIN OUTCOME MEASURES Patients' self-reported mood, anxiety, and externalizing symptoms along with independent clinical ratings of adaptive functioning. RESULTS Clinicians' prototype diagnoses showed small to moderate correlations with patient-reported psychopathology and performed as well as or better than DSM-IV diagnoses. Prototype diagnoses from independent interviewers correlated on average r = .50 and showed substantial incremental validity over DSM-IV diagnoses in predicting adaptive functioning. CONCLUSIONS Prototype matching is a viable alternative for psychiatric diagnosis. As in research on personality disorders, mood and anxiety disorder prototypes outperformed DSM-IV decision rules in predicting psychopathology and global functioning. Prototype matching has multiple advantages, including ease of use in clinical practice, reduced artifactual comorbidity, compatibility with naturally occurring cognitive processes in diagnosticians, and ready translation into both categorical and dimensional diagnosis.