Investigation of the pathogenesis of alcoholism in humans using different methodological approaches has facilitated detection of important biological factors of consequent metabolic diseases, endocrine disorders, and other medical conditions, such as alcoholic cardiomyopathy, alcoholic hypertension, heart and vascular lesions, alcoholic liver disease, alcoholic pancreatitis, etc. Alcohol abuse leads to damage to the nervous system, which can result in neurological and mental disorders, including alcoholic polyneuropathy, psychosis, and alcohol dementia. The complexity and versatility of the harmful effects of regular alcohol consumption on the human body can be considered in the perspective of a chronobiological approach, because alcohol is chronotoxic to biological processes. As a rhythm regulator, melatonin exerts a wide range of different effects: circadian rhythm regulation, thermoregulation, sleep induction, antioxidant, immunomodulatory, and anti-stress ones. This review presents from a chronobiological perspective the impact of melatonin on alcohol intoxication in terms of mental disorders, sleep and inflammation, hepatic injury, and mitochondrial function. It discusses the main clinical effects of melatonin on alcohol injury and the main targets as a therapy for alcohol disorders. Chronobiological effects of ethanol are related to melatonin suppression that has been associated with, among others, cancer risk. Exogenous melatonin seems to be a promising hepato- and immune-protector due to its antioxidant and anti-inflammatory properties, which in combination with other medicines makes it useful to prevent alcoholic organ damage. The reason for the scientific interest in melatonin as a treatment for alcoholism is obvious; the number of cases of this pathology that gives rise to metabolic syndrome, and its subsequent transformation into steatohepatitis, liver fibrosis, and cirrhosis, is increasing worldwide. Melatonin not only exerts antioxidant effects but it exerts various other effects contributing to the management of liver conditions. This review discusses the interaction between normal and pathological processes caused by alcohol consumption and the relationship between alcohol and melatonin in these conditions.