Positron emission tomography (PET) and combined PET/CT provide powerful metabolic and anatomical information together in a single exam. This article reviews the fundamentals of PET physics, the state of the art and future directions in PET technology, and the current clinical applications of PET. The latter is quite diverse and includes oncology, cardiology, neurology, and infection and inflammation imaging, all with FDG as the tracer. Additionally, novel radiopharmeuticals are under development, many of which are target cellular processes that are more specific than glucose metabolism.