Anxiety is a complex emotional state associated with sustained heightened autonomic and behavioral arousal and an increase in avoidance behavior. Anxiety-related behavior is a form of risk assessment behavior that is associated with a level of uncertainty or unpredictability regarding the outcome of emotionally salient events, often when both rewarding and aversive outcomes are possible. In this review, we highlight recent advances in our understanding of the neural circuits regulating anxiety states and anxiety-related behavior with an emphasis on the role of brainstem serotonergic systems in modulating anxiety-related circuits. In particular, we explore the possibility that the regulation of anxiety states and anxiety-related behavior by serotonergic systems is dependent on a specific, topographically organized mesolimbocortical serotonergic system that originates in the mid-rostrocaudal and caudal parts of the dorsal raphe nucleus.