The processing and regulation of fear is one of the key components of posttraumatic stress disorder (PTSD). Fear can involve both acute and potential threats that can manifest in different behaviors and result from activity within different neural nodes and networks. Fear circuits have been studied extensively in animal models for several decades and in human neuroimaging research for almost 20 years. Therefore, the centrality of fear processing to PTSD lends the disorder to be more tractable to investigation at the level of brain and behavior, and provides several observable phenotypes that can be linked to PTSD symptoms. Moreover, psychophysiological metrics of fear conditioning offer tools that can be used to shift diagnostic paradigms in psychiatry toward neurobiology-consistent with a Research Domain Criteria approach to PTSD. In general, mammalian fear processing can be divided into fear learning (or acquisition), during which an association develops between previously neutral stimuli and aversive outcomes, and fear extinction, in which the latter associations are suppressed by a new form of learning. This review describes translational research in both fear acquisition and extinction, along with their relevance to PTSD and PTSD treatment, focusing specifically on the empirical value and potential clinical utility of psychophysiological methods.