Electrochemical cell-based biosensors have attracted increasing interest within the last 15 years, with a large number of reports generally dealing with the sensors' sensitivity, selectivity, stability, signal-to-noise ratio, spatiotemporal resolution, etc. However, only a few of them are now available as commercial products. In this review, technological advances, current challenges, and opportunities of electrochemical cell-based biosensors are presented. The article encompasses emerging studies on cell-based biological field-effect devices, cell-based impedimetric sensors, and cell-based microelectrode arrays, mainly focusing on the last five years (from 2016 to mid-2021). In addition, special attention lies in recent progress at the single-cellular level, including intracellular monitoring with high spatiotemporal resolution as well as integration into microfluidics for lab-ona- chip applications. Moreover, a comprehensive discussion on challenges and future perspectives will address the future potential of electrochemical cell-based biosensors.