Development of new excitatory connectivity and decreases in γ-aminobutyric acid (GABA)ergic inhibition are mechanisms underlying posttraumatic epileptogenesis in animal models. Experimental strategies that interfere with these processes, applied between the trauma and seizure onset, are antiepileptogenic in the laboratory, and have promise for prophylaxis of epileptogenesis after cortical injury in humans. For an expanded treatment of this topic see Jasper's Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books).