Significant progress has been achieved in the field of solid-state biosensors over the past 50 years. Various sensing devices with high-density integration and flexible configuration, as well as new applications for clinical diagnosis and healthcare, have been developed using blood, serum, and other body fluids such as sweat, tears, and saliva. A high-density array of ion-sensitive field effect transistors was developed by exploiting the advantages of advanced semiconductor technologies and commercialized in combination with an enzymatic primer extension reaction as a DNA sequencer in 2011. Different types of materials such as inorganic materials, metals, polymers, and biomolecules are mixed together on the surface of the gate while maintaining their own functions; therefore, compatibility among different materials has to be optimized so that the best detection performance of solid-state biosensors, including stability and reliability, is achieved as designed. Solid-state biosensors are suitable for the rapid, cost-effective, and noninvasive identification of biomarkers at various timepoints over the course of a disease.