Appetitive instrumental discrimination learning procedures provide for CAM (cue and manipulandum) when the reward cue (discriminative stimulus positively correlated with positive reinforcement) is located at the response manipulandum (object that when contacted or manipulated defines the performance of the instrumental response). Evidence reviewed shows that CAM induces excessive and compulsive instrumental responding relative to otherwise comparable non-CAM control procedures. In humans, symptoms of drug abuse are particularly likely when the drug-taking implement (response manipulandum at which instrumental drug-taking is directed) is also predictive of the drug's rewarding effects (reward cue). Evidence that the predictive relationship between a drug-taking implement and drug reward relates to drug abuse is reviewed, and implications for treatment and prevention are considered. CAM is related to neurobiological models of drug abuse that emphasize the role of the neurotransmitter dopamine (DA). CAM produces convergence of DA-mediated responding for conditioned reinforcement with DA mediation of psychomotor activation and incentive-motivational processes to yield reflexive cue-directed responding not observed in non-CAM controls.