Many see the periaqueductal gray (PAG) as a region responsible for the downstream control of defensive reactions. Here we provide a detailed
review of anatomical and functional data on the different parts of the PAG together with the dorsal raphe, which completes the circle of periaqueductal nuclei. Based on anatomical features, we propose a new subdivision of the periaqueductal gray that accounts for the distinct characteristics of the area. We provide a comprehensive functional view of the periaqueductal gray, going beyond simple panic and escape to integrate data on fear, anxiety, and depression. Importantly, we conclude that this periaqueductal cluster of nuclei is broadly involved in motivated behavior controlling not only aversive but also appetitive behavior and with some involvement in more complex motivational processes such as approach-avoidance conflict resolution. In sum, these highly conserved nuclei surrounding the aqueduct appear to be the simplest, foundational, elements of integrated motivated goal-directed control of all types.