Cue-reactivity, or self-reported craving response to drug-associated stimuli, is an active area of research on factors that maintain drug use, particularly cigarette smoking. A common rationale for this research is the expectation that treatments that extinguish cue-induced craving will be effective as smoking cessation interventions. Therefore, the importance of research on the variables that moderate and control cue-induced craving would seem to hinge upon the relevance of cue-induced craving to nicotine dependence, particularly its association with relapse risk. However, the limited relevant clinical research has not demonstrated clearly a link between smoking relapse risk and self-reported craving in response to smoking cues. Links between relapse and other responses to cues, such as heart rate or electrodermal activity, are inconsistent or not significant. The Food and Drug Administration (FDA)-approved smoking cessation medications have not been shown to alleviate cue-induced craving, although they do alleviate abstinence-induced craving, which has been associated with relapse risk. Nevertheless, other acute measures assessed in the laboratory have been shown to predict subsequent relapse risk in quitting smokers, demonstrating the feasibility of this type of study. Future research may benefit from using more reliable and valid multi-item craving measures, focusing upon more specific conditions under which cue-induced craving may predict relapse and, most importantly, considering dependent measures other than self-reported craving in response to cues, particularly actual smoking behavior. Without stronger evidence in support of the relevance of cue-induced craving response to the persistence of smoking behavior or other measures of dependence, it will be incumbent upon researchers in this area to justify why studies of cue-induced craving contribute to our understanding of dependence.