Ion‐sensitive field effect transistor (ISFET) sensor is a hot topic these years, playing the combined roles of signal recognizer and converter for (bio)chemical analytes. In this review article, the basic concept, origination, and history of the ISFET sensor are presented. In addition, the common fabrication processes, the most‐used working principle (potentiometric, amperometric, and impedancemetric), and the techniques of gate functionality (physical, chemical, and biological) are discussed introducing the afterward signal transfer processes from ISFET to the terminals through different types of circuits. At last, the development and recent progress (until 2021) of ions and biomolecules (DNA molecules, antibodies, enzymatic substrates, and cell‐related secretions or metabolism) were introduced together with the outlook and facing obstacles (Debye screening, the wearability of ISFET, the multiplexed detections) before the commercialization of ISFET. This review article emphasizes the advantages of the developed ISFET sensors as miniaturization, low‐cost, all‐solid, highly sensitive, and easy operation for portable and multiplexed detections.