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The role of CNS neuromodulators in cognitive neurorehabilitation can be related to two main issues: (1) the negative impact on cognition of drug categories prescribed for different neurologic symptoms, such as spasticity, extrapyramidal symptoms, or epileptic seizures; (2) their possible role in neuroprotection and amelioration of the cognitive status of the patient, especially attention and memory. This paper reviews different pharmacological aspects of cognitive neurorehabilitation in epilepsy.