Biosensors based on the microbial fuel cell (MFC) platform have been receiving increasing attention from researchers owing to their unique properties. The lithotrophic MFC, operated with a neutrophilic iron-oxidizing bacterial community, has recently been developed and proposed to be used as a biosensor to detect iron, and likely metals in general, in water samples. Therefore, in this review, important aspects of the lithotrophic MFC-based biosensor, including its configuration, fabrication, microbiology, electron transfer mechanism, sensing performance, etc. were carefully discussed in comparison with those of heterotrophic (organotrophic) counterparts. Particularly, the challenges for the realization of the practical application of the device were determined. Furthermore, the application potentials of the device were also considered and positioned in the context of technologies for metal monitoring and bioremediation.