We will detail several CMOS SPAD photodetectors for use in a range of high-energy and nuclear physics applications, implemented at EPFL’s AQUA Lab in collaboration with external partners. The requirements are often quite different, e.g. high timing precision and detection at low event rates in time-of-flight positron emission tomography (ToF-PET), possibly requiring 3D-stacked implementations, very high data rates, spatial granularity, and photon-starved operation in ring imaging Cherenkov counters at colliders (RICH), or the coupling of sensors to scintillating fibers as active neutrino targets with a dedicated hybrid architecture. High photon detection efficiency in the visible is often required, along with tiling capability to achieve large surfaces. Operation in hostile environments is often needed as well, such as low or even cryogenic temperatures and/or high radiation levels.