Anxiety disorders clearly have learned and non-learned components, suggesting that both types of animal models are of potential relevance. Defensive fear and anxiety behaviors have been extensively studied in rodents, using behavioral paradigms that test such behaviors in response to both learned and innately threatening stimuli. This chapter reviews these studies of learned fear and innate anxiety, detailing the latest advances in the understanding of neurobiological mechanisms and their implications for treatment. It also considers data from human studies to examine the relevance of these animal models of normative defensive behaviors to the pathological anxious behaviors seen in patients with anxiety disorders. Generalized anxiety disorder (GAD) offers perhaps the most compelling case for the relevance of innate anxiety, in that patients worry about numerous aspects of their lives without any logical rationale or previous experience.