Photon-counting spectral CT requires accurate and efficient detection of photons across the broad x-ray spectrum. MARS photon-counting spectral CT imaging is an emerging technology on the clinical horizon, providing a highly specific 3D material imaging at high spatial and energy resolution. This new modality, driven by photon-processing detectors, enables the characterization of biological tissues, their composition and physiological processes, and perform a quantified assessment of exogenously administered multiple heavy atom contrast agents simultaneously. Current research projects utilizing the MARS scanners have successfully demonstrated novel applications of photon-counting spectral imaging. The aim of this chapter is to provide an overview of MARS imaging technology and its applications of small animal and human specimens.