Photon counting detectors (PCDs) have revolutionized micro-computed tomography (micro-CT) imaging technology by directly converting incident X-ray photons into electrical signals, eliminating intermediate scintillation steps. This advancement enables high-resolution, multi-energy CT imaging with reduced electronic noise, enhanced contrast sensitivity, and lower radiation doses compared to conventional systems. By resolving individual photon energies, PCDs allow simultaneous identification and quantification of multiple materials through spectral techniques, providing deeper insights into a sample’s composition and spatial distribution. Current applications span biomedical research, preclinical studies, and clinical diagnostics, while emerging innovations in detector efficiency and AI-driven processing promise broader future utility. This chapter examines the fundamental principles of PCDs, evaluates their current and emerging applications in PCD-based micro-CT systems, and addresses the key advancements, challenges, and transformative implications of these technologies for precision medicine and materials science.