Different methods have been developed in clinical abuse liability testing in man. Tolerance, psychic and/or physical dependence must be investigated through clinical studies during drug development of a new substance. Adequate methodology is needed using double-blind, time-blind evaluations, comparisons of different dose levels and duration of treatment for a given drug, abrupt and gradual interruption of treatment, appropriate period of observation after treatment cessation ... The optimal scale to evaluate properly the symptoms occurring after drug discontinuation is still under investigation. These studies will or should permit the differentiation of rebound, withdrawal and recurrence. Methods developed to study reinforcing effects in post-addicts and healthy subjects are self-administration and choice procedures. In addition, the more traditional approach has been through assessing self-reported effects in which standardized questionnaires are used (Addiction Research Center Inventory or A.R.C.I.; Single Dose Questionnaire or S.D.Q.). A third focus of measurement has been discrimination studies performed in individuals with histories of drug abuse as well as healthy subjects. Abuse-liability testing of a new compound needs a multidimensional assessment to optimize the predictivity in defining the relative risk.