It is well known that the subthalamic nucleus (STN) plays an important role in regulating motor function, but recent studies suggest the STN is also involved in regulating motivated behavior. For example, bilateral lesions of the STN increase motivation for both food and cocaine as assessed by 'breakpoint' on a progressive ratio schedule. However, the psychological mechanism(s) by which STN lesions increase motivation for rewards is unknown. We hypothesized that STN lesions might influence one specific component of motivation, the attribution of incentive value (incentive salience) to reward-related cues. We tested this hypothesis by quantifying the ability of a discrete cue that had been paired with the non-contingent delivery of either food or cocaine to elicit approach towards it (ie, to produce a 'sign-tracking' conditioned response, CR). STN lesions made prior to training increased asymptotic levels of sign-tracking behavior directed towards a cue paired with either food or cocaine. In addition, when STN lesions were made after animals had already undergone Pavlovian training, and animals were tested under extinction conditions, the STN lesion still facilitated a sign-tracking CR. Finally, reintroduction of the US (food) following extinction immediately restored robust sign-tracking behavior in animals with STN lesions. We speculate, therefore, that the STN is part of a neural system that moderates the amount of incentive salience attributed to reward-related stimuli. Activity in this neural system may help mitigate the development of compulsive behavioral disorders, such as addiction, which are characterized by pathological control over behavior by reward-associated cues.