This chapter reviews advances and novel techniques presented in past years to improve the efficiency of one relevant bioelectrochemical system, the microbial fuel cell (MFC). The efficiency of MFCs, when energy production is considered, has reached a limit: Several paths have been followed to further increase the possibilities. Here, we will concentrate on genetic engineering approaches to improve efficiency by altering metabolic pathways that channeled electrons from its production in the intracellular metabolic process to the electrode surface. These paths include small molecules, as well as large proteins, such as cytochromes. Modification of the limiting step (if any) or the whole electron path is the goal. We will present in this chapter advances made in the most used microorganisms (such as Geobacter and Shewanella), as well as other heterotrophic and autotrophic organisms. The selection of natural and synthetic microbial communities at the anode is also discussed.