Chemical sensors can be used to analyze a wide variety of environmental and biological gases and liquids and may need to be able to selectively detect a target analyte. Different methods, including gas chromatography, chemiluminescence, selected ion flow tube, and mass spectroscopy, have been used to measure biomarkers. These methods show variable results in terms of sensitivity for some applications and may not meet the requirements for a handheld biosensor. A promising sensing technology utilizes AlGaN/GaN high electron mobility transistors (HEMTs). HEMT structures have been developed for use in microwave power amplifiers due to their high two dimensional electron gas (2DEG) mobility and saturation velocity. The conducting 2DEG channel of AlGaN/GaN HEMTs is very close to the surface and extremely sensitive to adsorption of analytes. HEMT sensors can be used for detecting gases, ions, pH values, proteins, and DNA. In this paper we review recent progress on functionalizing the surface of HEMTs for specific detection of glucose, kidney marker injury molecules, prostate cancer, and other common substances of interest in the biomedical field.