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This paper reviews the recent progress of HEMT-based microsensors for physical, chemical and biological applications, describes the challenges faced, and also points out the future trends and opportunities in this field. Additionally, the close proximity of the conducting 2DEG (two-dimensional electron gas) HEMT channel to the surface provides enhanced sensitivity to adsorption of substances, while the miniaturization and high-frequency operation capability of HEMT-based microsensors enables their seamless integration into wireless sensor networks for remote monitoring of patient’s health through bedside or handheld instrumentation. The reliable operation of wide-bandgap HEMT (High Electron Mobility Transistor) devices at elevated temperatures up to 400☌, along with their less vulnerability to thermal or optical excitation, combined with their greater resistance to chemical corrosion by acids and alkalis, has encouraged researchers to make endeavours towards the development of a family of sensors for harsh environments, an area where conventional silicon MOSFET (metal-oxide-semiconductor field-effect transistor) and ISFET (ion-sensitive field-effect transistor) devices are rendered ineffective.