Some substance dependent individuals (SDI) suffer from a decision-making impairment akin to that seen in neurological patients with lesions of the ventromedial (VM) prefrontal cortex. The somatic-marker hypothesis posits that decision-making is a process that depends on emotion and that deficits in emotional signaling will lead to poor decision-making. In this study, we tested the hypothesis that SDI who perform disadvantageously on a decision-making instrument, the gambling task (GT), have a deficit in the somatic signals that help guide their decision in the advantageous direction. Since deficits in decision-making/somatic markers can also result from dysfunctional amygdala, we asked indirectly (i.e. via tests sensitive to VM or amygdala dysfunction) whether such a deficit in SDI is restricted to VM dysfunction or includes the amygdala. Using the GT, and skin conductance response (SCR) as an index of somatic state activation, we studied groups of SDI (n=46), normal controls (n=49), and VM patients (n=10). A subgroup of SDI showed defective performance on the GT coupled with impaired anticipatory SCR, but normal SCR to punishment, and normal acquisition of conditioned SCR to an aversive loud sound. This supports the hypothesis that the poor decision-making in some SDI is associated with defective somatic state activation that is linked to a dysfunctional VM cortex. Thus, the dysfunctional VM cortex underlying the "myopia" for the future in some SDI may be one of the principle mechanisms underlying the transition from casual substance taking to compulsive and uncontrollable behavior.