Positron emission tomography (PET) with 2-[18F]-fluorodeoxyglucose (FDG) has been widely used for the evaluation of cortical glucose metabolism in several neurodegenerative disorders while its potential role in the evaluation of cortical and subcortical activity during task in healthy and pathological brain remain still matter of debate. Few studies have been carried out in order to investigate the potential role of this radiotracer for the evaluation of brain glucose consumption during dynamic brain activation. The aim of this review is to provide a general overview of the applications of FDG PET in the evaluation of cortical activation at rest and during tasks, first describing the physiological basis of FDG distribution in brain and its kinetic in vivo. An overview on the imaging protocols and image interpretation will be provided as well. As a last aspect, the results of the main studies in this field will be summarized and the results of PET findings performed in healthy subjects and patients suffering of various diseases will be reported.