The nuclear medical imaging methods, positron emission tomography (PET) and single photon emission computed tomography (SPECT), utilize the detection of gamma rays leaving the body after a radioactive tracer has been administered. The sensitivity of PET allows the detection of picomolar tracer amounts in vivo and current technology offers millimeter (PET) or submillimeter (SPECT) spatial resolution. These techniques are used in clinical and preclinical applications. The basic principles of gamma ray detection and image generation in PET and SPECT are summarized in this chapter. Furthermore, effects causing degradation of image quality are discussed.