This chapter reviews the relative abuse liability of the various stimulant medications used to treat impairments associated with chronic sleep deprivation and how the drugs' potential for abuse impacts their medical usefulness. The abuse liability of a drug is an important consideration during the drug development process, when estimating risk: benefit ratios for approving drugs, and ultimately in the prescription and utilization of a drug by physicians and patients. The physicochemical properties of a drug determine how it may be administered and its pharmacokinetic profile. The mesolimbic dopamine system has been identified as a key pathway involved in mediating the properties of drugs that are responsible for their addictive nature. The behavioral effects of drugs evaluated in abuse liability studies include reinforcing effects and discriminative stimulus effects. Amphetamine is readily self-administered and discriminated by animals, and often used as a positive control drug in studies of abuse liability.