Microbial fuel cells (MFCs) have been conceived and intensively studied as a promising technology to achieve sustainable wastewater treatment. However, doubts and debates arose in recent years regarding the technical and economic viability of this technology on a larger scale and in a real-world applications. Hence, it is time to think about and examine how to recalibrate this technology's role in a future paradigm of sustainable wastewater treatment. In the past years, many good ideas/approaches have been proposed and investigated for MFC application, but information is scattered. Various review papers were published on MFC configuration, substrates, electrode materials, separators and microbiology but there is lack of critical thinking and systematic analysis of MFC application niche in wastewater treatment. To systematically formulate a strategy of (potentially) practical MFC application and provide information to guide MFC development, this perspective has critically examined and discussed the problems and challenges for developing MFC technology, and identified a possible application niche whereby MFCs can be rationally incorporated into the treatment process. We propose integration of MFCs with other treatment technologies to form an MFC-centered treatment scheme based on thoroughly analyzing the challenges and opportunities, and discuss future efforts to be made for realizing sustainable wastewater treatment. Broader context Our society's expectations for wastewater treatment have evolved over time. While protecting aquatic environment and public health continues to be a paramount concern, the desire to recover clean water, energy and useful resources from wastewater is getting increasingly stronger today. This increased demand on wastewater treatment has stimulated intensive research for sustainable treatment technologies. Microbial fuel cell (MFC) has been regarded as a promising technology to serve this goal, but low power density, high cost and difficulty in reactor scaling-up severely limit its development and give rise to debates about its practical feasibility. Here, we provide critical rethinking about the challenges and opportunities of this technology, and propose a more promising avenue for MFC development-through integration with other enhanced treatment and resource recovery technologies for more sustainable wastewater treatment. The advantages of such an MFC-centered treatment system in terms of energy consumption, environmental footprint, operating stability and economics are analyzed, and an exemplary process ow is presented.