Around half the inmates in prison institutions have antisocial personality disorder (ASPD). A recent theory has proposed that a dysfunction of the endogenous opioid system (EOS) underlies the neurobiology of borderline personality disorder (BPD). In the present theoretical paper, based on a comprehensive database and hand search of the relevant literature, this hypothesis is extended to ASPD, which may be the predominant expression of EOS dysfunction in men, while the same pathology underlies BPD in women. According to evidence from human and animal studies, the problematic behaviours of persons with antisocial, callous, or psychopathic traits may be seen as desperate, unconscious attempts to stimulate their deficient EOS, which plays a key role in brain reward circuits. If the needs of this system are not being met, the affected persons experience dysphoric mood, discomfort, or irritability, and strive to increase binding of endogenous opioids to receptors by using the rewarding effects of aggression by exertion of physical or manipulative power on others, by abusing alcohol or substances that have the reward system as target, by creating an endorphin rush by self-harm, by increasing the frequency of their sexual contacts, or by impulsive actions and sensation seeking. Symptoms associated with ASPD can be treated with opioid antagonists like naltrexone, naloxone, or nalmefene. Copyright (c) 2015 John Wiley & Sons, Ltd.