Medical imaging instrumentation is mostly based on the use of luminescent materials coupled to optical sensors. These materials are employed in the form of granular screens, structured crystals, single transparent crystals, ceramics, etc. Storage phosphors are also incorporated in particular X-ray imaging systems. The physical properties of these materials should match the criteria required by the detective systems employed in morphological and functional biomedical imaging. The systems are analyzed based on theoretical frameworks emanating from the linear cascaded systems theory as well as the signal detection theory. Optical diffusion has been studied by different methodological approaches, such as experimental measurements and analytical modeling, including geometrical optics and Monte Carlo simulation. Analysis of detector imaging performance is based on image quality metrics, such as the luminescence emission efficiency (LE), the modulation transfer function (MTF), the noise power spectrum (NPS), and the detective quantum efficiency (DQE). Scintillators and phosphors may present total energy conversion on the order of 0.001–0.013 with corresponding DQE in the range of 0.1–0.6. Thus, the signal-to-noise ratio, which is crucial for medical diagnosis, shows clearly higher values than those of the energy conversion.