Publisher Summary This chapter introduces the basic ideas of Positron Emission Tomography (PET), including the design and function of PET systems. The designs for PET systems can be separated into three main groups of applications. This includes, small animal imaging, neurological imaging, and whole-body imaging. The goal of PET is to generate images of the distribution of positron emitters in vivo. PET systems rely on the detection of annihilation gamma rays that follow positron decay. The gamma rays are detected in coincidence by detectors that surround the patient. This chapter also discusses issues of scanner geometry and their effect on count rate. The spatial resolution of PET imaging is limited by the fundamental nature of positron annihilation, positron range, noncolinearity, detector point-spread function (PSF), and finally parallax error. To improve spatial resolution, improvements in system sensitivity are required in addition to higher resolution detector arrays. One technology that aids in this quest is depth of interaction (DOI) detector systems. A DOI system is designed to give information about the depth in the crystal at which an interaction takes place, and the system designer can exploit that information to correct parallax errors.