Although metabolic abnormalities in the orbitofrontal cortex have been observed in substance dependent individuals (SDI) for several years, very little attention was paid to the role of this brain region in addiction. However, patients with damage to the ventromedial (VM) sector of the prefrontal cortex and SDI show similar behaviors. (1) They often deny, or they are not aware, that they have a problem. (2) When faced with a choice to pursue a course of action that brings an immediate reward at the risk of incurring future negative consequences, they choose the immediate reward and ignore the future consequences. Studies of patients with bilateral lesions of the VM prefrontal cortex support the view that the process of decision-making depends in many important ways on neural substrates that regulate homeostasis, emotion, and feeling. Parallel lines of study have revealed that VM cortex dysfunction is also evident in subgroups of individuals who are addicted to substances. Thus, understanding the neural mechanisms of decision-making has direct implications for understanding disorders of addiction and pathological gambling, and the switch from a controlled to uncontrolled and compulsive behavior. On the clinical front, the approach to treat addictive disorders has been dominated by a diagnostic system that focuses on behaviors, physical symptoms, or choice of drugs. The article emphasizes the concept of using neurocognitive criteria for subtyping addictive disorders. This is a significant paradigm shift with significant implications for guiding diagnosis and treatment. Using neurocognitive criteria could lead to more accurate subtyping of addictive disorders, and perhaps serve as a guide for more specific, and potentially more successful, behavioral and pharmacological interventions.