Solution gate field-effect transistors (SGFETs) based on diamond show great potential in biosensing and bioelectronics thanks to the advantageous combination of physical and chemical properties offered by this carbon material. In this contribution, we discuss fundamental aspects of diamond SGFETs as well as a number of important applications. We first demonstrate how the p-type charge accumulation at the hydrogen-terminated diamond surface can be controlled with an electrolyte gate, forming the basis of diamond SGFETs. For a proper understanding of the operation of the surface conductive diamond SGFETs, it is essential to consider the effect of such a hydrophobic surface on the structure of water at the diamond/electrolyte interface. The electronic transport in the p-type surface conductive channel is studied with Hall-effect experiments performed in an electrolyte in order to elucidate the limiting scattering mechanisms for carriers at the diamond surface. We present the fabrication and characterization of arrays of solution-gated field effect transistors based on single crystalline diamond revealing attractive sensor properties such as high sensitivity and low electronic noise. These diamond SGFETs are investigated as sensors of pH and ionic strength of the electrolyte. Further, we demonstrate the use of these devices for the detection of neurotransmitters when the sensor's active area is functionalized with suitable enzymes. Finally, we show the application of diamond SGFETs for the extracellular recording of the electrical activity of electrogenic cells, thus paving the way for the development of novel diamond-based bio-hybrid systems with the potential to facilitate further progress in the understanding of the cell–semiconductor interface.