In the presurgical assessment of drug refractory partial epilepsies PET represents a privileged means for investigating glucose metabolism and neurotransmission in the functional-deficit zone, defined as the region of cortex that is functioning abnormally in the interictal period. Another aim of PET investigation is to produce images of neurotransmission abnormalities underlying neuronal hyperexcitability, and thus to allow direct visualization of the epileptogenic zone. This approach has been mostly based on the binding of various radio-ligands on specific receptors (GABA-A, opiate and serotonin receptor) and on brain uptake of serotonin precursors. These attempts have not yet been fully validated, in spite of promising studies of serotonin synthesis and receptors. Consequently, at the present state of their development, most of the PET techniques routinely used, reflect changes that are not directly related to the epileptogenic process itself. The lack of large multicentric controlled studies, evaluating the impact of PET, represents the main limitation to a better understanding of the clinical role and utility of PET in epilepsy. We review the basic aspects and limitations of the technique, the various radiopharmaceuticals that have been tested in epilepsy, the sensitivity of the different types of PET investigations, the pathophysiology of PET abnormalities and discuss the practical utility of PET imaging in presurgical assessment of partial epilepsies.