This chapter provides a comprehensive overview of the routine quality control (QC) program of instrumentation used within a nuclear medicine department, in particular for positron emission tomography (PET/CT and PET/MR) scanners. In particular, it describes the importance of performing these tests to verify the performance of the equipment throughout its lifetime. Several recommendations by national and international agencies exist for periodic PET/CT and PET/MR QC. In particular, the NEMA documents allow the evaluation and comparison of different clinical PET scanners, with the purpose of provide standard procedures that allow, in an objective manner, the evaluation of the characteristics of PET tomographs. In addition, the chapter describes the recommendations for basic routine QC tests that should be scheduled and carried out for the PET scanners and for the additional tests for hybrid systems, in particular for CT and MR scanners.