OBJECTIVE: It is recommended that the psychological status of adolescents with diabetes be assessed periodically as part of ongoing care. The World Health Organization-Five Well-Being Index (WHO-5) is a short self-report instrument that appears suitable for this purpose. This study is the first to assess the reliability and validity of the WHO-5 in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Ninety-one adolescents with type 1 diabetes (aged 13-17 years) from four pediatric clinics completed the WHO-5, along with other psychological measures: the Center for Epidemiologic Studies Depression Scale (CES-D), the Diabetes Family Conflict Scale (DFCS), and the mental health and self-esteem subscales of the Child Health Questionnaire (CHQ-CF87). Confirmatory factor analysis (CFA) and exploratory factor analysis were conducted. Readability, homogeneity, and item-total and inter-item correlations were determined. Concurrent validity was examined by calculating correlation coefficients among all measures. Sensitivity and specificity of the WHO-5 were tested against those for the CES-D using receiver operating characteristic (ROC) curves. RESULTS: CFA confirmed the one-factor structure; Cronbach's alpha of this 5-item scale was 0.82. The WHO-5 showed a moderate to strong correlation with the CES-D (r = -0.67), with the mental health (r = 0.60) and self-esteem (r = 0.43) subscales of the CHQ-CF87, and with the DFCS (r = -0.34), confirming concurrent validity. ROC curve analysis confirmed the WHO-5 cutoff point of <50 for identification of mild to severe depressive affect (sensitivity 89% and specificity 86%). CONCLUSIONS: The WHO-5 is a brief, patient-friendly measure of positive well-being with good psychometric properties that appears suitable for routine use in adolescents with type 1 diabetes.