The goal of the current study was to determine whether activation of the mirror neuron system, as measured by mu rhythm desynchronization, varied as a function of image content in smokers compared with nonsmokers. EEG activity was recorded while participants passively viewed images depicting smoking-related and nonsmoking-related stimuli. In half of the images, cues were depicted alone (inactive), while for the remaining images, cues were depicted with humans interacting with them (active). For the nonsmoking stimuli, smokers and nonsmokers showed greater mu suppression to the active cues compared to the inactive cues. However, for the smoking-related stimuli, smokers showed greater perception-action coupling for the active cues as reflected in their enhanced mu suppression, compared to nonsmokers. The results of the current study support the involvement of the perceptual-motor system in the activation of motivated drug use behaviors.