The research on microbial fuel cells (MFCs) needs various knowledge of different fields such as electrochemistry, microbiology, environmental engineering, and material engineering. Although electrochemically active bacteria are very diverse, the performance of MFCs is affected primarily by the structure of the reactor system. Thus, the development in the system architecture is critical to lower internal resistance and increase power generation for commercialization. This paper summarizes the principles of MFCs and demonstrates the infinite potential of MFCs in various applications including wastewater treatment, biosensors, biohydrogen production, remote power sources, implantable medical devices, etc.