In the last decade, single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been characterized by relevant technological innovations, with relevant improvements of both software and hardware settings, having the main goal of establishing systems with higher sensitivity and resolution, and with the potential to allow high quality images despite a more favorable dosimetry. In this regard, the introduction of dedicated cardiac cameras equipped with high-efficiency Cadmium–Zinc–Telluride (CZT) detectors have represented a milestone, allowing the unprecedented reduction of acquisition times. Moreover, the increased spatial resolution and count sensitivity and the possibility to acquire in list mode, like in PET exams, allow the quantification of myocardial blood flow that can potentially change the use of myocardial scintigraphy by CZT camera, in particular in difficult patients. The present article will review the existing evidence on SPECT imaging with dedicated CZT cameras, describing the technical characteristics of these cameras and shedding light on the latest fields of application of CZT imaging.