Ischemic brain damage occurs through all age subgroups, ranging from the newborn to the elderly, but with predominance in more aged brains either in animals or in humans. The present understanding of the pathophysiological mechanisms of ischemic brain damage suggests that, despite different age and its consecutive changed molecular behavior to ischemic states, there is a common underlying cascade of events. But, there exists an age-dependent influence on stroke of which the few existing experimental data are complex: the immature brain is, in fact, less resistant to hypoxic-ischemic brain damage than its adult counterpart. The intermediate age subgroup is more tolerant to hypoxic-ischemic brain damage than either very young or more mature ages. In addition, the neuroprotective mechanism of ischemic preconditioning is also influenced by this different molecular behavior to cerebral ischemia within the different age subgroups. The authors put these findings from experimental or clinical studies into the context of the current knowledge of ischemic preconditioning of the brain and discuss their relevance for experimental and clinical research. From the present data, it seems that neuroprotection of preconditioned brain in different age subgroup is not the result of any difference in the extent of the underlying cascade of ischemic events but rather the result of different sensitivity to ischemic preconditioning in different age subgroups.