The fundamental mechanisms of brain function are being revealed by studies ranging from molecular to systems levels of analysis. Studying the connections between brain regions at the cellular level is an essential link in this endeavor. Growing evidence points to highly specific circuit organization, with rules for both local and long-range connectivity between different cell types. This specificity may underlie the functions of different cell types, brain regions and ultimately larger networks. An understanding of this organization is particularly important for the prefrontal cortex (PFC) and basolateral amygdala (BLA) which play a key role in emotion and motivation and consequently are implicated in numerous diseases including, autism, anxiety disorders and addiction. In this essay, I discuss studies of the circuits linking the BLA and PFC in the mouse using a combination of anatomy, electrophysiology and optogenetics. First, I identify three distinct populations of projection neurons in the BLA and determine that among these the PFC selectively drives projections to the PFC and ventral hippocampus over projections to nucleus accumbens (NAc). Next, I examine BLA input to the PFC, finding that the BLA predominantly inhibits superficial layers of PFC via activation of two interneuron classes. Additionally, both BLA and interneuron inputs are stronger at BLA projecting neurons than NAc projecting neurons. These findings contribute substantial evidence to the existence of remarkably specific connections within and across brain regions.