Abuse liability testing involves an evaluation of the likelihood of drug self-use and also an evaluation of the harmful effects of drug use. This paper reviews the rationale and utility of examining performance and physiological measures in clinical abuse liability evaluation. It is concluded that there are three important reasons to employ such measures in abuse liability studies: (1) to serve as a reference point to allow for between drug and across measure comparisons; (2) to directly quantify dose-response functions on multiple dimensions of drug effect and thus evaluate the overall profile of effects; and (3) to provide information on the likelihood that drug use will produce harmful effects. The review illustrates each of these purposes and briefly summarizes conclusions from previous studies employing performance and physiological measures in the abuse liability evaluation of sedatives, stimulants, and opioids.