Biological fuel cells have attracted increasing interest in recent years because of their applications in environmental treatment; energy recovery and small scale power sources. Microbial Fuel Cell (MFC) is a promising technology for efficient wastewater treatment, generating energy as direct electricity for onsite applications, and recovering resources such as nutrients and heavy metals. Enzyme based fuel cells are of particular interest in biomedical research and healthcare; in environmental monitoring, and as the power source for portable electronic devices. The technology developed for fabrication of enzyme electrodes is described. Different enzyme immobilization methods using layered structures with self-assembled monolayers and entrapment of enzymes in polymer matrixes are reviewed. The performances of enzymatic biofuel cells are summarized and approaches on further development to overcome current challenges are discussed. This innovative technology will have a major impact and benefit to medical science and clinical research, healthcare management and energy production from renewable sources. Applications and advantages of using MFC for wastewater treatment are described: including organic matter removal efficiency, electricity generation, and resource recovery. The performance of organic removal, nutrients, and heavy metals recovery from municipal wastewater and real industrial wastewater are summarized. In addition, H2 and acetate production from microbial electrochemical cells are also reviewed to highlight the commercial implementation and challenge of this technology.