Studies of the response of rodents to predatory odors (mainly cat) have provided useful insights into the nature of defensive behavior. This article reviews work in this area with a focus on a behavioral paradigm recently developed in our laboratory in which we present rats with a piece of fabric collar that has been previously worn by a cat. Rats presented with this stimulus spent most of their time engaged in a behavior we call 'head out' in which the rat pokes its head out from a hide box and scans the environment. Periodic 'flat back approaches' and 'vigilant rearing' towards the cat odor source are seen as well as inhibition of non-defensive behaviors such as locomotor activity and grooming. Cat odor causes a sustained increase in blood pressure (> 15mm Hg) without greatly affecting heart beat rate. Rats will develop conditioned fear to both contexts and cues that have been paired with cat odor. C-fos immunohistochemistry indicates that cat odor selectively activates a defensive behavior circuit involving the medial amygdala, ventromedial and dorsomedial hypothalamus, dorsal premammillary nucleus and the periaqueductal gray. The defensive response to cat odor is attenuated by acute administration of the benzodiazepine midazolam (0.375 mg/kg), with chronically administered SSRI antidepressants and acute alcohol exerting more modest anxiolytic effects. The behavioral response to cat odor is very different to that seen to trimethylthiazoline (TMT: fox odor) which has effects more like those seen to an aversive putrid odor. It is concluded that cat odor is a useful tool for elucidating behavioral, neural, pharmacological and autonomic aspects of defensive behavior and anxiety.