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Sensor systems based on piezoresistors have found a wide variety of applications whenever mechanical stress due to external mechanical input is to be determined. Such sensor elements are fabricated using commercial CMOS processes enabling the realization of highly integrated systems with electronics for signal amplification and multiplexing. They combine stress-sensing elements such as Wheatstone bridges, 4- and 8-terminal well-based devices, or 4-contact piezoresistive field effect transistors, i.e. piezo-FETs. In addition, innovative devices generating out-of-plane current components are applied to determine out-of-plane stress components. The paper discusses the sensing elements, the system architecture and the post-CMOS fabrication processes required to realize the CMOS-integrated stress sensor systems. Smart orthodontic brackets and a stress sensing neural probe are discussed in more detail.