Membrane proteins play a vital role in biological function and have tremendous potential in microsystem array platforms utilizing bioelectrochemical methods for continuous use, label-free detection. To achieve this potential, challenges in membrane interfaces, on-CMOS electrode arrays, CMOS instrumentation electronics, and the integration of these technologies must be addressed. This paper outlines these challenges and summarizes recent developments toward membrane protein biosensor arrays on CMOS. A tethered bilayer lipid membrane with embedded alkali ion-channel protein is shown as example interface compatible with on-chip biosensor array realization. The development of on-CMOS electrode arrays and insulating layers capable of linking membrane protein interfaces with CMOS electronics is described. Finally, recent developments in CMOS instrumentation circuits for electrochemical impedance spectroscopy and multiple voltammetry measurements are presented. Together, these accomplishments demonstrate the viability of microsystem platforms utilizing membrane proteins.