The rat is probably the most-studied species both in behavioral neuroscience in general as well as in studies of brain plasticity. A discussion of the organization and plasticity of the prefrontal cortex (PFC) of rodents is therefore germane to the general topic of the current volume. Nonetheless, controversy remains over the question of whether the frontal regions of the rodent can legitimately be viewed as relevant models of prefrontal cortical organization in primates (e.g. Preuss, 1995). One problem with the rat is that the behavioral repertoire of rodents would appear to be considerably simpler than that of primates. To the extent that the prefrontal regions of primates are involved in the complex executive functions, it is therefore critical to determine if rodents even have such behavioral processes. A second problem with the rat as a prefrontal model is that the gross organization and cytoarchitecture of the frontal cortical regions of rodents and primates show some marked differences. For example, whereas layer IV of the PFC of primates is distinctly granular in appearance, layer IV is virtually absent in the rat frontal cortex. Consider too, that the volume of the cerebral cortex of a rat is about a hundred times smaller than that of the cerebral cortex of a rhesus monkey, and about a thousand times smaller than that of a human being (Uylings and Van Eden, 1990). A thorough discussion of issues relating to homology and brain organization are beyond the scope of this chapter, but before examining the organization and plasticity of the PFC of rats, it will be necessary to at least superficially consider the question of rodent-primate comparisons. We then review the functional organization of the PFC of the rat before considering the nature of frontal cortical plasticity in rats. As might be anticipated, we shall argue here that the rat is an excellent model for studying frontal functions and plasticity in humans and other primates.