Over the past few decades, considerable research has been conducted on field-effect transistor (FET) biosensors; however,other than electrochemical sensors for pH, they have not reached the commercialization stage and still remain at the basicresearch level. Although several reports have been published on experiments with real biological samples, no reports exist ofdevelopments that have reached commercialization or finalized approval for use. In this paper, we explain the reason for theexperiments of FET biosensors to induce spurious signals in an experimental setup and explain the existence of misunderstandingsregarding the operating principle of FET biosensors owing to the spurious signals. Based on the thoughtfulreview of the results of previously published papers, we show that the electrochemical read-out principle of FET biosensorsrequires our intensive understanding of the interfacial potential between the solution and the sensor electrode for further progressin the FET biosensor research.