Silicon nanowire field-effect transistors (Si-NW FETs) have been demonstrated as a versatile class of potentiometric nanobiosensors for real time, label-free, and highly sensitive detection of a wide range of biomolecules. In this review, we summarize the principles of such devices and recent developments in device fabrication, fluid integration, surface functionalization, and biosensing applications. The main focus of this review is on CMOS compatible Si-NW FET nanobiosensors.