What are the conceptual and empirical bases for current interventions for acute stress reactions following trauma exposure? This review compares the two major alternatives to managing acute stress reactions, outlines their conceptual bases and critiques the evidence for their efficacy in preventing subsequent stress disorders. The review integrates current evidence for cognitive behavior therapy with recent neuroscience findings that fear reduction learning can be enhanced by modulating glutamatergic systems. D-cycloserine provides exciting opportunities to enhance the effects of cognitive-behavioral therapy, and points to closer understanding of the biological mechanisms that underpin clinical gains achieved by psychological therapies.