Laboratory models of prolonged seizures and status epilepticus in developing animals demonstrate age- and model-dependent propensity for brain injury. Even in models without overt brain injury, plasticity, which leads to epileptogenicity as well as to behavioral and cognitive effects, has been demonstrated. Brief, recurrent seizures in the neonatal period not only appear to exhibit plasticity that can be anatomically and physiologically meaningful but also seem to produce cognitive deficits. Translation of these findings into clinical practice is limited by the effects chronic therapy may have on brain development. There is little evidence that available treatments can effectively alter epileptogenesis. However, it is widely agreed that prolonged seizures and status epilepticus can carry negative consequences. Preventing epileptogenesis remains an important goal to modify the development of comorbidities, and it represents an area of research in need of much progress. For now, prevention of prolonged seizures with early intervention is important and is the most effective available option to minimize the potential short- and long-term adverse effects of prolonged seizures and optimize patient outcomes.