Though there has been significant progress in research related to microbial fuel cells (MFCs), there are still a number of challenges that need to be overcome in order to commercialize this technology. There is a need to address the low power generation and wastewater treatment efficiency and higher cost associated with the fabrication of MFCs. This chapter is aimed to throw light on the status of the present investigations on MFCs focusing on the different operational and design parameters. The most promising future directions in MFC research to make this system efficient in terms of power generation, wastewater treatment, and reducing fabrication costs are also identified.