This paper describes the rationale for use of preclinical assessments of abuse liability in laboratory animals, and then discusses "cross-cutting" methodological issues that apply to behavioral evaluations intended to contribute to an abuse liability evaluation package. Issues include use of: (1) positive and negative control conditions; (2) full dose-effect evaluations, (3) multiple dependent measures, (4) pharmacokinetic evaluations to guide choice of dose ranges, (5) a species for which good methodological and comparative data are available to aid interpretation of results, and (6) appropriate methods for the group or single-subject experimental design selected. The remainder of the paper describes basic methodology by which three core pieces of behavioral data required by the Food and Drug Administration for its use in the overall abuse liability analysis can be obtained preclinically. Reinforcing effects are assessed in study of drug self-administration; drug discrimination assesses degree of overlap of interoceptive stimulus effects with relevant comparison drugs; physical dependence potential is determined by assessing whether a withdrawal syndrome occurs after chronic drug administration. Background and methodological issues specific to each procedure are discussed. A key consideration for cross-cutting and specific methodological issues is that choices made enable confident interpretation of both positive and negative results.