Publisher Summary Transgenic mouse models hold promise for elucidating the genetic basis of human pathophysiological conditions including addiction, schizophrenia, and dementia. These disorders typically involve changes in the regulation of emotion, behavioral flexibility, working memory, and decision making, behaviors that are critically dependent on different regions of the prefrontal cortex (PFC). The ability to use precise molecular genetic tools to study the cellular mechanisms underlying PFC function has resulted in a sudden increase in the use of mice in the study of brain and behavior. A very little is known about the structural organization of the mouse PFC including its morphology, and its connections with other brain regions. In addition, behavioral studies in mice depend critically on behavioral paradigms that are available to assess complex cognitive and emotional functions. The functional organization of the mouse PFC leans heavily on extrapolations from the rat PFC. This chapter reviews the anatomical and functional organization of the mouse prefrontal cortex. Consistent with the rat, anatomical staining techniques other than Nissl, such as SIM-32 and AChE clearly define boundaries between the dorsal, medial and orbital regions of the mouse PFC. Patterns of connectivity between selective PFC regions and cortical and subcortical structures reliably identifies specific cortical zones in the mouse PFC.