Photon-counting imaging technology has applications in many fields such as fluorescence lifetime imaging microscopy (FLIM), time-resolved Raman spectroscopy, 3D imaging, and even space communications. The requirement to detect single photons with picosecond temporal resolution makes single-photon avalanche photodiode (SPAD) a popular choice. Advanced biomedical imaging applications such as pill cameras, retinal prosthesis, and implantable biocompatible monitoring sensors require a compact image system, which can be implanted into a living body. To meet these requirements, novel single-photon image sensor solution needs to be developed, in which new substrate post-processing and backside illumination or even dual-side illumination are core technologies, with inherent CMOS compatibility as a prerequisite. This chapter proposed and demonstrated the world’s first flexible CMOS single-photon avalanche diode image sensor, providing a suitable solution for implantable biomedical imaging or monitoring applications, and wherever a curved imaging plane is essential.