The current study tested whether the amplitude of the P3 event-related potential (ERP) elicited by smoking cues is (a) associated with the degree of self-reported craving reactivity, and (b) moderated by degree of tobacco dependence. Because alcohol and cigarettes are frequently used together, and given recent evidence indicating that individual differences in alcohol sensitivity influence reactivity to alcohol cues, we also investigated whether alcohol sensitivity moderated neural responses to smoking cues. ERPs were recorded from young adult smokers (N = 90) while they participated in an evaluative categorization oddball task involving 3 types of targets: neutral images, smoking-related images, and images of drinking straws. Participants showing larger P3 amplitudes to smoking cues and to straw cues (relative to neutral targets) reported greater increases in craving after cue exposure. Neither smoking status (daily vs. occasional use) nor psychometric measures of tobacco dependence consistently or specifically moderated P3 reactivity to smoking cues. Lower alcohol sensitivity was associated with larger P3 to smoking cues but not comparison straw cues (relative to neutral targets). This effect was further moderated by tobacco dependence, with the combination of lower sensitivity and higher dependence associated with especially pronounced P3 reactivity to smoking cues. The findings suggest the smoking-cue elicited P3 ERP component indexes an approach-oriented incentive motivational state accompanied by a subjective sense of cigarette craving. Self-reported low sensitivity to the pharmacologic effects of alcohol may represent a marker of drug cue reactivity and therefore deserves attention as a potential moderator in smoking cue exposure studies.