Sertraline is a selective serotonin reuptake inhibitor that is approved by the U.S. Food and Drug Administration for the treatment of major depression, obsessive-compulsive disorder (in adults and children), and panic disorder. Although numerous studies have found sertraline to be very effective in the treatment of anxiety, there have been few case reports of panic attacks actually being induced by treatment with sertraline. In this article, we present the cases of two patients without any personal or family history of anxiety disorders who developed panic attacks shortly after the initiation of sertraline therapy. We will also review the literature in regard to the development of anxiety symptoms during treatment with the newer antidepressants and discuss the neurochemical basis of these antidepressant-induced panic attacks.