Nuclear medicine deals with the noninvasive visualization of functional and metabolic processes of the human body. Nuclear imaging techniques are based on the injection of a radiopharmaceutical consisting of a radionuclide that is chemically linked to a molecule with a well-characterized biological behavior. The photons emitted from radionuclide decay are then detected by the imaging device, which allows the determination of a three-dimensional distribution of the tracer within the body. The most used instrument in clinical nuclear medicine is the gamma camera. This instrument continues to be widely used for planar imaging and single-photon emission computed tomography (SPECT). Together with SPECT, the growth of positron emission tomography (PET) was remarkable in recent years. In addition, other instruments used in nuclear medicine include various detectors and counters, such as dose calibrators primarily used to measure radioactivity levels before administering radiopharmaceuticals to patients, counters for monitoring low radiation levels, and gamma well counters used in radioimmunoassay and for measuring radioactivity levels in various samples. The detection mechanism, design, and working principles of imaging instrumentation for nuclear medicine are described. The focus of this chapter is the underlying principles and components of the gamma camera, SPECT, and PET instrumentations, as well as other detectors used in nuclear medicine imaging.