Animal models of associative threat learning provide a basis for understanding human fears and anxiety. This talk explores the successes and failures in translating the neural mechanisms of threat processing identified in animal models to complex human learning and the treatment of anxiety-related disorders. First, I will briefly review how extinction and emotion regulation, techniques adapted in cognitive behavioral therapy treatments can be used to control learned defensive responses via inhibitory signals from the ventromedial prefrontal cortex to the amygdala. One drawback of these techniques is threat responses are often weakly inhibited and can return, which has been proposed to underlie the significant relapse rate following cognitive behavioral therapies.