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Chronic and excessive alcohol consumption can result in structural and functional brain abnormalities mainly affecting the frontocerebellar circuit and the Papez circuit in alcoholic patients. When present, this brain damage is linked with graded neuropsychological deficits such as deficits of executive functions, episodic memory, and emotional processes. The contribution of these neuropsychological deficits to relapse has been investigated in cross-sectional and longitudinal studies. Cross-sectional studies show that impairments of executive functions and episodic memory may reduce the benefit of motivational therapy and behavioral treatment. Longitudinal studies suggest that, among other factors, several neuropsychological deficits may contribute to relapse. Further longitudinal studies are required to provide a better understanding of the role of brain damage and neuropsychological deficits in relapse. Those factors need to be explored in combination with social or environmental variables to improve the detection of alcoholics at risk of relapse.