The development of alcohol dependence is the result of a combination of various factors. Psychosocial and psychiatric conditions, together with functional alterations of the brain or genetic traits, contribute to the development of problems related to alcohol use or alcohol dependence. Clinical studies using neuroimaging techniques (PET, fMRI) and preclinical studies using different animal models of problems related to ethanol consumption have improved our knowledge of the neurochemical mechanisms involved in alcohol dependence. These studies have served to identify peptides or receptors modified by ethanol consumption, which are functionally altered in strains of rats or mice highly vulnerable to ethanol consumption. Such peptides or receptors may be interesting targets for the treatment of alcoholism. Among the different targets studied in recent years, the opioid and cannabinoid systems meet a number of conditions for eligibility as candidates for the treatment of alcohol dependence. The μ-opioid receptor and cannabinoid CB1 receptor, in particular, are affected by ethanol consumption. In clinical studies, genetic polymorphisms of the μ-opioid and CB1 receptors have been associated with increased vulnerability to alcohol consumption. Similarly, functional alterations in μ-opioid and cannabinoid receptors have been identified in specific strains of rats or mice with high preference to ethanol consumption. Furthermore, several studies have shown that the manipulation of these receptors using agonists or antagonists may increase or decrease ethanol consumption, which confirms the validity of these receptors as targets for the treatment of alcohol dependence. In this review, we analyzed the genetic traits and psychiatric and/or psychosocial conditions that affect vulnerability to and the pharmacologic treatment of alcohol dependence, with special emphasis on the role of opioid and cannabinoid receptors. The use of animal models as important tools for identifying neurochemical mechanisms relevant to understanding and treating alcohol use problems was evaluated. Peer Reviewed