Positron emission tomography (PET) is assuming increasing importance as a clinical and investigative functional imaging modality. Cerebral blood flow determination with PET is now more easily performed due to improvement in tomography design, increased speed and ease of data analysis, and improvement in radiopharmaceutical synthesis and delivery. This article reviews the historic development of the PET, the evolution of cerebral blood flow measurement techniques with PET, technical considerations in PET imaging, radiopharmaceuticals for cerebral blood flow determination, and tracer kinetic models used for cerebral blood flow determination. Representative examples of PET cerebral blood flow imaging are shown and the evolving applications to brain mapping are discussed.