Post-traumatic epilepsy (PTE) remains one of the most intractable consequences of traumatic brain injury (TBI) and its incidence and characteristics have remained relatively constant through the past century, in spite of significant advances in medical management. Survivors of military penetrating head injury (PHI) suffer by far the highest incidence of (PTE), ranging from 32% to 55%, and they are a particularly valuable group in which to study this complication. Clues to the high incidence of PTE in PHI survivors are likely related to dural penetration with free intracerebral blood, and perhaps to retained ferric metal fragments. The failure of well-reasoned and well-conducted trials evaluating conventional anticonvulsants for prevention of PTE also offers important clues and has forced us to reconsider our approach to management. Here we briefly review the clinical characteristics of PHI patients with PTE, with an emphasis on clues to pathogenesis that can generalize to other types of head injury; followed by a discussion of the pathogenetic mechanisms common to epilepsy, PHI, and TBI in general, with an eye to future neuroprotection and PTE prophylaxis. Future studies that more directly target the basic pathogenesis of TBI, including neuroinflammation and lipid peroxidation with their consequent excitotoxic mechanisms and aberrant regeneration, may ultimately prove to be more fruitful in the struggle to understand and control this especially stubborn complication of head injury.