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Studies of neurological patients with focal lesions involving ventromedial prefrontal cortex (vmPFC) have demonstrated a critical role for this brain area in various aspects of cognition, emotion, and behavior. In this article, we review the key themes, methods, and findings from neuropsychological research on vmPFC lesion patients. Early case studies demonstrated profound disruptions in personality and behavior following vmPFC damage, including blunted affect, poor decision-making, and inappropriate social behavior. Subsequent laboratory investigations with groups of vmPFC lesion patients have revealed deficits in a host of interrelated functions, such as value-based decision-making, future and counterfactual thinking, physiological arousal to emotional stimuli, emotion recognition, empathy, moral judgment, and memory confabulation. The compendium of findings described here demonstrates that vmPFC is crucial for diverse aspects of adaptive function.Review of human lesion studies of vmPFC.vmPFC damage associated with dramatic changes in personality and behavior.Deficits in affect, decision-making, social conduct/cognition, and memory.Functional impact of vmPFC lesion etiology, laterality, and age onset are discussed.vmPFC is critical for diverse aspects of adaptive function.