Here, we explore if microbial fuel cell (MFC) technology can replace activated sludge processes for secondary wastewater treatment. We will discuss the present limitations and problems of electric current generation when a complex wastewater is treated with a diverse and undefined community of microbes in large-scale systems. These challenges include low coulombic efficiencies, slow kinetic rates, and nonlinear power density increases during scale-up efforts. Finally, we developed a prediction of the main economic gain from treating wastewater with microbial fuel cells. We conclude that electricity generation will not justify MFC operation, but that BOD removal with this more sustainable technology is attractive.