The continuous development of SPECT over the past 50 years has led to improved image quality and increased diagnostic confidence. The most influential developments include the realization of hybrid SPECT/CT devices, as well as the implementation of attenuation correction and iterative image reconstruction techniques. These developments have led to a preference for SPECT/CT devices over SPECT-only systems and to the widespread adoption of the former, strengthening the role of SPECT/CT as the workhorse of Nuclear Medicine imaging. New trends in the ongoing development of SPECT/CT are diverse. For example, whole-body SPECT/CT images, consisting of acquisitions from multiple consecutive bed positions in the manner of PET/CT, are increasingly performed. Additionally, in recent years, some interesting approaches in detector technology have found their way into commercial products. For example, some SPECT cameras dedicated to specific organs employ semiconductor detectors made of cadmium telluride or cadmium zinc telluride, which have been shown to increase the obtainable image quality by offering a higher sensitivity and energy resolution. However, the advent of quantitative SPECT/CT which, like PET, can quantify the amount of tracer in terms of Bq/mL or as a standardized uptake value could be regarded as most important development. It is a major innovation that will lead to increased diagnostic accuracy and confidence, especially in longitudinal studies and in the monitoring of treatment response. The current work comprises two main aspects. At first, physical and technical fundamentals of SPECT image formation are described and necessary prerequisites of quantitative SPECT/CT are reviewed. Additionally, the typically achievable quantitative accuracy based on reports from the literature is given. Second, an extensive list of studies reporting on clinical applications of quantitative SPECT/CT is provided and reviewed.