The sensor is the part of the detector where the X-ray interaction takes place, and the signal that is measured by the electronics originates. Here a comprehension of the photon/sensor interaction and charge cloud generation must be obtained to understand the sensor’s behavior. Also, understanding the subsequent charge cloud transport and signal generation mechanisms is needed. The details of these processes are discussed in this chapter, starting with the photon/sensor interaction mechanisms present in semiconductor sensors. The operation of any radiation detector depends on how the radiation interacts with the sensor material of the detector. The interaction needs to cause a measurable change in the physical properties of the sensor, typically a change in the number of free carriers available to conduct current. Electronic circuits then measure and further process this change in sensor property to extract information about the detected photon. The subject of this chapter pertains to the detection of X-rays and γ-rays using semiconductor sensors and the associated front-end electronics. More specifically, a largely qualitative treatise on the physics and principles of hybrid and monolithic pixel detectors is given.