Resources scarcity and electricity demand have been dramatically increasing. Wastewater is recognized as one of resources for water, energy and plant fertilizing nutrients. Nevertheless, current wastewater treatment technologies have limitations due principally to their energy- and cost-intensive for achieving the conversion target of wastewater recovery. It is desired to develop a new technology to generate alternatives to conventional energy sources in a sustainable manner. An innovative technology based on the use of microbial fuel cells (MFCs) has been proved as a critical pathway for bioconversion processes towards electricity generation, then for addressing energy and environmental problems. Three special features including energy saving, less sludge production and less energy production make MFCs outstanding compared with the existing technologies. Multiform wastewaters could be efficiently degraded through advancing MFCs alone or integrating MFCs with other processing units. However, the low power density and the high operating cost of MFCs have greatly limited their applications on large-scale problems, and then result in some debates and doubts about their development and applications. Therefore, this paper objectively discussed the problems and applications of MFCs in wastewater treatment. Moreover, the integration of MFCs with other treatment processes was presented to verify the practicality and effectiveness of MFCs in contaminants removal. Furthermore, the primary challenges and opportunities for scaling-up and future applications of MFCs in wastewater were analyzed.