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98 reviewsResearch on mental health has traditionally separated the study of ill-being, including clinically defned mental and behavioural disorders Check for updatesand subthreshold problems, from the study of well-being, which encompasses factors such as life satisfaction and positive afect. Although previous reviews of studies primarily using self-report scales indicate that ill-being and well-being are distinct yet interconnected constructs, a deeper examination of their relationship is lacking. In this Perspective, we synthesize genetic, biological, developmental, psychosocial, societal, cultural and clinical research on ill-being and well-being. Our review reveals substantial genetic overlap and similar biological underpinnings for ill-being and well-being. By contrast, environmental factors and societal changes often exert divergent infuences. We propose a diferentiated multidisciplinary framework in which the shared and unique determinants, predictors, mechanisms and consequences of mental ill-being and well-being vary across levels of analysis, ofering a more nuanced understanding of the interconnections.