Microbial fuel cells (MFCs) are fascinating alternative energy sources that can remediate waste streams (e.g., municipal water streams), while producing usable energy. A typical MFC consists of anodic and cathodic chambers that are usually separated by an ion-exchange membrane. The membrane prevents anolytes and catholytes from crossing to the opposite chambers while selectively and efficiently transferring certain ions from one compartment to the other in order to support redox reactions and charge balancing. The use of a membrane enables close electrode placement in non-microfluidic MFCs, which can have a significant impact on the internal resistance, thus improving power output. For example, recently a "near zero gap distance" flow-MFC produced very high-power density at around 8.8 W m when electrodes were sandwiched between a 106 µm anion exchange membrane which selectively transported hydroxide and better mitigated pH imbalance between the electrodes. Much effort has been expended in improving the membrane for high performance (ion selectivity and throughput), but for microfluidic MFCs, their role in preventing anolyte/catholyte mixing is considered less critical because mass transport across laminar coflow interfaces is strictly diffusion limited, and therefore slow. However, in practice, anolyte/catholyte solution crossover can arise during long experiments due to pump instabilities or during solution source replacement or other maintenance operation. Even under ideal flow conditions, simulations have shown that electrode spacing of less than 4 mm can result in more than 10% of the inlet acetate concentration diffusing to the cathode. Oftenoverlooked, solution crossover may therefore present a major challenge in realizing the potential advantages of microfluidic MFCs, especially in relation to the fabrication devices with closely spaced electrodes.