Rationale: Motivational drive and its underlying affect-related states are the core mechanisms that precede the seeking and taking of drugs in substance dependence. Objective: The present study aimed to investigate the motivational relevance of cocaine cues and whether or not an appetitive emotional system is involved employing event-related potential (ERP) measurements. Methods: Cocaine-addicted subjects and healthy controls were exposed to neutral and cocaine-related pictures whilst ERPs were recorded simultaneously over frontal, parietal and midline sites. Results: Patients exhibited ERP amplitude discrepancies between neutral and cocaine-related pictures for N300, late slow positive wave (LSPW) and sustained slow positive wave (SSPW), whilst this effect was absent in control subjects. Differences in neutral and cocaine cue-evoked ERP waves were also found at left frontal sites for LSPW and SSPW in the patient group only. No group-specific cue-evoked ERP amplitudes were observed at parietal and midline sites. Conclusion: The findings confirm the assumption that cocaine cues induce motivational relevance in cocaine-dependent individuals. It is possible that exposure to cocaine cues triggers an appetitive emotional system since left frontal sites are assumed to be involved in processing positive emotional-laden stimuli. The present study provides evidence that the sensitivity of ERP correlates for cocaine cues may be an indicator of motivational and emotional processes in drug-dependent individuals. © Springer-Verlag 2004.