Two nuclear medicine-based approaches to functional brain imaging can be used to study the pediatric population, positron emission tomography (PET) and single-photon emission computed tomography (SPECT). This chapter talks about PET instrumentation, positron-emitting radiotracers, and radiotracer modeling. It describes the PET methods used to measure cerebral blood flow (rCBF) and cerebral blood volume (rCBV) and glucose and oxygen metabolism. Measurements of CBF glucose metabolism are widely used as indices of neuronal activity. The radionuclides used in SPECT decay by emitting a single photon or gamma ray from their nucleus; radioactivity distribution is estimated by detection of gamma rays. To interpret changes in PET and SPECT studies, it is necessary to understand the relationships among CBF, metabolism, and local neuronal activity. Radiation exposure in the context of PET and SPECT is an important consideration when they are used for research rather than diagnostic purposes.