Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop following exposure to a traumatic event, in approximately 10% of individuals exposed. This disorder is characterized by an exacerbation of the fear response that can be explained by dysfunctional learning and memory in vulnerable individuals. Over the years, Pavlovian fear conditioning has emerged as a powerful paradigm for studying the neural foundations of aversive associative memory formation and has provided a better understanding of the underlying neurobiological changes in PTSD. In the first part of this article, we present a summary of the vulnerability factors associated with the early development of PTSD, focusing on the role of stress hormones in the formation and consolidation of traumatic memories. We show that dysfunctions at different levels of the glucocorticoid-signaling cascade are present in vulnerable individuals and that treatment with hydrocortisone, a glucocorticoid agonist, given during the first hours after traumatic exposure, protects against the development of PTSD in a modest but significant way. We then discuss the limitations of the fear conditioning model and its biological correlates (neuroendocrinology of stress) to explain the etiology of PTSD, a heterogeneous disorder in both its symptomatic expression and the variety of pathways associated with its development. The fear-conditioning model, while having the advantage of being translational, only explains one facet of the complex neurobiology of PTSD and does not appear to provide a sufficient conceptual framework to result in improved treatments for PTSD in an afflicted population.