It has been suggested that drug cue-elicited urges and psychophysiological reactions are the results of Pavlovian conditioning processes and that it should be possible to extinguish these responses with cue exposure with response prevention. It has already been shown that subjective cue-elicited urges can be extinguished, but it is unclear whether this is also true for cue-elicited psychophysiological arousal. This was tested in the present study in a heterogeneous sample of drug and alcohol dependent patients. It was found that cue-elicited urges can indeed be extinguished. However, such a clear pattern of extinguished cue reactivity was not found for the psychophysiological measures. Furthermore, the extinction of drug urges was not specific for cue exposure treatment. It is concluded that cue-elicited psychophysiological arousal does not underlie subjective cue reactivity and may not reflect Pavlovian conditioned drug responding.