Anterior cingulate cortex (ACC) hypoactivations during cognitive processing characterize drug addicted individuals as compared with healthy controls. However, impaired behavioral performance or task disengagement may be crucial factors. We hypothesized that ACC hypoactivations would be documented in groups matched for performance on an emotionally salient task. Seventeen individuals with current cocaine use disorders (CUD) and 17 demographically matched healthy controls underwent functional magnetic resonance imaging during performance of a rewarded drug cue-reactivity task previously shown to engage the ACC. Despite lack of group differences in objective or subjective task-related performance, CUD showed more ACC hypoactivations throughout this emotionally salient task. Nevertheless, intensity of emotional salience contributed to results: (i) CUD with the largest rostroventral ACC [Brodmann Area (BA) 10, 11, implicated in default brain function] hypoactivations to the most salient task condition (drug words during the highest available monetary reward), had the least task-induced cocaine craving; (ii) CUD with the largest caudal-dorsal ACC (BA 32) hypoactivations especially to the least salient task condition (neutral words with no reward) had the most frequent current cocaine use; and (iii) responses to the most salient task condition in both these ACC major subdivisions were positively intercorrelated in the controls only. In conclusion, ACC hypoactivations in drug users cannot be attributed to task difficulty or disengagement. Nevertheless, emotional salience modulates ACC responses in proportion to drug use severity. Interventions to strengthen ACC reactivity or interconnectivity may be beneficial in enhancing top-down monitoring and emotion regulation as a strategy to reduce impulsive and compulsive behavior in addiction.