Localization of eloquent cortical regions is an important aspect of neurosurgical practice. When lesions lie close to or within areas such as somatosensory, motor or language cortex, the goal of surgical treatment is maximal resection without causing neurological deficit. Hence precise functional mapping combined with accurate delineation of the extent of pathology is important for deciding whether surgery is feasible at all and defining the safe limit of resection and the optimal operative approach. In addition, when the electroclinical pattern of intractable seizures suggests a specific localization in sensorimotor cortex (e.g., seizures originating in the face area), functional mapping may be of use in directing the surgical treatment at the seizure focus. Activation studies using positron emission tomography (PET) and the tracer [(15)O] labeled water ([(15)O]H(2)O) can be used in presurgical planning and in intraoperative surgical guidance in individual patients. The use of PET technology for these purposes is critically dependent on advances in registration or alignment of images acquired using different modalities; the development of neurosurgical guidance devices; and the development of methods of statistical analysis suitable for use in single subjects.