Although approximately 90% of the U.S. population will experience a traumatic event within their lifetime, only a fraction of those traumatized individuals will develop posttraumatic stress disorder (PTSD). In fact, approximately 7 out of 100 people in the U.S. will be afflicted by this debilitating condition, which suggests there is substantial inter-individual variability in susceptibility to PTSD. This uncertainty regarding who is susceptible to PTSD necessitates a thorough understanding of the neurobiological processes that underlie PTSD development in order to build effective predictive models for the disorder. In turn, these predictive models may lead to the development of improved diagnostic markers, early intervention techniques, and targeted treatment approaches for PTSD. Prior research has characterized a fear learning and memory network, centered on the prefrontal cortex, hippocampus, and amygdala, that plays a key role in the pathology of PTSD. Importantly, changes in the function, structure, and biochemistry of this network appear to underlie the cognitive-affective dysfunction observed in PTSD. The current review discusses prior research that has demonstrated alterations in brain function, structure, and biochemistry associated with PTSD. Further, the potential for future research to address current gaps in our understanding of the neural processes that underlie the development of PTSD is discussed. Specifically, this review emphasizes the need for multimodal neuroimaging research and investigations into the acute effects of posttraumatic stress. The present review provides a framework to move the field towards a comprehensive neurobiological model of PTSD.