Self-powered biosensors (SPBs) based on enzymatic biofuel cells (EFCs) and microbial fuel cells (MFCs) have attracted considerable attention due to their obvious advantages such as simple configuration and ease of miniaturization, and potential applications including clinical diagnosis, environmental monitoring, industrial process control, etc. In this review, we will summarize the recent advances in SPBs, focusing on the use of EFC-SPBs as power sources in combination with microelectronic and electrochromic devices, and the applications of MFC-based SPBs as sensors for detecting toxicity, chemical oxygen demand (COD), biochemical oxygen demand (BOD) and assimilable organic carbon (AOC). The efforts in, for example, boosting the energy, reducing the cost, and improving the sensing performance in terms of sensitivity, accuracy and dynamic detection range are discussed. Finally, future prospects for the development of MFC-based SPBs are presented.