This chapter provides an in-depth reference for hybrid imaging such as positron emission tomography – Computed Tomography (PET-CT) and single photon emission computed tomography - Computed Tomography (SPECT-CT), a powerful diagnostic tool that integrates anatomical and functional imaging to enhance diagnostic accuracy and clinical decision-making. It begins with a discussion on the need, evolution, and advantages of hybrid imaging, followed by detailed coverage of radiation detectors and detection mechanisms used in SPECT, PET, and CT systems. A major focus is placed on PET, tracing its historical development, principles of coincidence detection, and evolution of PET-CT technology. The chapter explores technical components such as detector design, 2D vs 3D acquisition, Time-of-Flight (TOF) detection, and total body PET scanners, with emphasis on performance characteristics and quality control measures including resolution, sensitivity, scatter correction, and image co-registration accuracy. It also covers the workings of the gamma camera and SPECT, explaining each component from collimators and scintillation crystals to image display and correction algorithms. A comprehensive section outlines quality control protocols, both intrinsic and extrinsic for gamma cameras and SPECT, along with tomographic accuracy and SPECT-CT co-registration techniques. Additionally, the chapter reviews image reconstruction methods such as filtered back projection (FBP), iterative reconstruction, and advanced techniques for fusion imaging. It concludes with a review of clinical applications across modalities, highlighting how PET-CT, SPECT-CT, PET-MRI, and even PET-CT-MRI.