Advances in neurobiological techniques are occurring at an astonishing rate. In many respects, study of drug self-administration happens in a similar manner to the initial studies nearly 40 years ago. If the sophisticated techniques available to neuroscience are to be used to help understand drug self-administration (and potentially drug use in humans), help explain some of the interesting findings, or find biological correlates of behavioral changes, then the behavioral models used need to be equally as sophisticated, interesting and dynamic. Data from two series of experiments will be presented and discussed with reference to neurobiological correlates of the behavioral differences. In monkeys, social housing and the establishment of dominance hierarchies was used to induce neurobiological changes that were then associated with differences in cocaine self-administration. In rats, various histories of self-administration result in animals that, for example, respond to considerably higher breakpoints maintained by cocaine on a progressive ratio schedule, relative to control animals. Neurobiological investigation of these groups of rats can help find biological correlates related to changes in the reinforcing efficacy of cocaine (which might be related to the development of addiction in humans). The overall focus of the presentation will be to strengthen the idea the behavioral scientists need to continue developing interesting behavioral models if we are going to try to use some of the neurobiological and molecular biological techniques that are being developed in other fields of science.