Introduction: The involvement of the opioidergic system in the pathogenesis of various addictive and non-addictive disorders has led to a renewed interest in expanding the clinical uses of opioid antagonists. Aim: To critically discuss the question whether opioid antagonists can be used in the management of psychiatric diseases, in association with, or as offering an alternative to, standard pharmacotherapy. Methods: To review past and current literature on the action displayed by opioid antagonists on a wide range of psychiatric diseases, while taking into account standard pharmacotherapy for the same psychiatric diseases. To compare the risk-benefit ratio of opioid antagonists with that of medications traditionally used in the same diseases. Results: Opioid antagonists should be considered a possible treatment choice in all those pathological behaviours that share an instinctive or impulsive nature. Such behaviours are both innate (sexual, aggressive, feeding) and acquired (drug-seeking, gambling), depending on the nature of the rewarding stimulus that reinforced them. On the other hand, opioid antagonists should be excluded from the treatment of all the external or internal conditions experienced by patients as punishing and ego-dystonic (as leading to anxiety, depression, obsessive thoughts). Conclusions: Opioid antagonists have proved to be suitable tools for the treatment of a wide range of addictive and non-addictive psychiatric diseases. In the specific case of the addictive diseases, they can be used to treat patients suffering from alcohol, cocaine, and cannabis use disorders, but also from pathological gambling, and to reverse potentially fatal opiate-related overdoses. In all forms of non-addictive diseases they can be used in the management of a first pure manic episode, negative symptoms of schizophrenia, self-injuring, some kinds of aggressiveness, autism, bulimia nervosa and binge eating disorder, when appropriate in association with standard pharmacotherapies.