This review aims to interpret and present data about methamphetamine effects in cerebral cortex. Studies in methamphetamine abusers, non-human primates as well as rodents’ models have shown a deleterious effect of methamphetamine on brain physiology to a great extent. Individual responses to the environment during methamphetamine intoxicated states and withdrawal periods involve a complex interplay between cortical and subcortical networks. Both acute and chronic methamphetamine administration toxic models have shown profound alterations in frontal and parietal cortices. Neurotoxicity involves variables of dopamine neural damage as well as other non-dopaminergic interneurons. Such methamphetamine effects seem long-lasting and concern a wide range of cognitive and behavioral functions, memory and inhibitory control. Here, behavioral and neurochemical evidences are discussed in light of possible pharamacological strategies to modulate methamphetamine long lasting effects on brain function.