Electrochemical sensing has been widely applied to a variety of applications involving disease diagnosis due to its ability to measure targets directly, fast response, and high accuracy compared to other detection methods. The accelerated uptake of point-of-care (POC) testing underscores the need for portable devices integrated with electrochemical sensing functions. Noninvasive electrochemical sensing has also been studied with regard to the analysis of bodily fluids and represents a promising method for long-term tracking of patient health conditions. A comprehensive understanding of electrochemical electrode and readout circuitry has led to increasing research on the use of electrochemical sensors for pharmaceuticals, biotechnology, and disease diagnosis applications. This article reviews the state-of-the-art electrochemical readout interfaces using CMOS technology for biomarker detection.