This chapter provides a comprehensive overview of the routine quality control (QC) program of instrumentation used within a nuclear medicine department, in particular for hybrid single-photon emission computed tomography (SPECT/CT) scanners. In particular, it describes the difference between acceptance and constancy tests and explains that these tests are required to check the performance of the equipment throughout its lifetime. Several recommendations by national and international agencies exist for periodic SPECT/CT QC. An effective QC program is able to detect subtle changes in the performance of the SPECT scanner, using simple, practical, and reproducible procedures, and through the use of selected and measurable parameters directly linked to the quality of clinical images; in other words, it helps to detect problems before they can impact clinical studies in terms of safety, image quality, quantify accuracy, and patient radiation dose. In addition, the chapter describes the recommendations for basic routine QC tests that should be scheduled and carried out for the main instruments of the nuclear medicine department. Also considering that the introduction in nuclear medicine of cadmium-zinc-telluride (CZT) detectors is considered one of the most significant innovations of recent years, in the chapter are described also the tests that can be adapted for 3D-ring CZT SPECT systems, because, at present, no specific standards are available. The NEMA NU 1-2018 standard could be used to evaluate the performance of these systems, although not all tests are fully applicable due to the systems’ characteristics.