Publisher Summary This chapter emphasizes on semiconductor detectors, which is an emerging alternative to conventional detectors. This chapter also discusses the application of room-temperature semiconductor detectors to nuclear medicine imaging. Two compound semiconductors are extensively researched in the field of medical imaging, astronomy, and general gamma-ray spectroscopy. This includes Cadmium telluride (CdTe) and cadmium-zinc-telluride (CdZnTe, or CZT). The appeal of this family of detector materials for nuclear medicine is based on several factors. Most important is the elimination of scintillation photons and the need for photomultiplier tubes (PMTs). Furthermore, this chapter reviews the history of these detectors and the research behind the important aspects of their performance. Charge transport and signal generation schemes have been studied by many groups, and the current work describes those efforts that most directly impact medical imaging performance. Recent efforts of medical imaging equipment manufacturers to create prototypes from these materials are presented, along with comments on their potential future use in the emerging field of molecular imaging.