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Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used in pediatric anesthesia. Recently, a series of animal studies have shown that ketamine may have neurotoxic effects on the developing brain and that these effects can later cause neurofunctional impairment. However, other studies have also shown that ketamine protects the central nervous system by inhibiting inflammation in the developing brain. The present study offers a review of the existing preclinical and clinical studies. We concluded that the role of ketamine varies not only on the basis of the dose and frequency of exposure but also the intensity of the noxious stimuli. Moreover, the repeated ketamine usage may be neurotoxic to immature brains in the absence of noxious stimuli, whereas it may be neuroprotective in the same brains in the presence of strong painful stimuli. Balancing the neurotoxic and neuroprotective effects of ketamine on the developing brain may be possible, but further study is required. The therapeutic window during which precritical surgeries can be performed remains undefined.