This paper is a critique of fixed and progressive ratio schedules used to examine the neural substrates of cocaine reinforcement. The discussion focuses on problems encountered while examining the effects of neurotoxic lesions and pharmacological pretreatments on cocaine reinforcement. We review the theoretical and interpretational problems associated with the use of the fixed ratio (FR) schedules that have been used in the majority of studies, and we conclude that rate of drug intake cannot directly address the issue of increased or decreased reinforcer efficacy. The progressive ratio (PR) schedule offers some advantages over FR schedules, although it is now clear that the same implementation cannot be applied across all drug classes. It is likely that the motivation to self-administer psychostimulant vs. opiate drugs is qualitatively different. We conclude that there is no single schedule that can quantify all aspects of drug reinforcement and that behavioral paradigms will need to be adapted according to the particular question under study.