It has been well established that alterations in polyamine metabolism are associated with animal models of global ischemia. Recently, this has been extended to include models of focal ischemia and traumatic brain injury. There is much evidence to support the idea that polyamines may play a multifaceted detrimental role following ischemia reperfusion. Due to the deficit of knowledge about their physiology in the CNS, the link between ischemia-induced alterations in polyamine metabolism and neuronal injury remains to be substantiated. With the recent revelation that polyamines are major intracellular modulators of inward rectifier potassium channels and certain types of NMDA and AMPA receptors, the long wait for the physiologic relevance of these ubiquitous compounds may be in sight. Therefore, it is now conceivable that the alterations in polyamines could have major effects on ion homeostasis in the CNS, especially potassium, and thus account for the observed injury after cerebral ischemia.