Self-powered electrochemical biosensors utilize biofuel cells as a simultaneous power source and biosensor, which simplifies the biosensor system, because it no longer requires a potentiostat, power for the potentiostat, and/or power for the signaling device. This review article is focused on detailing the advances in the field of self-powered biosensors and discussing their advantages and limitations compared to other types of electrochemical biosensors. The review will discuss self-powered biosensors formed from enzymatic biofuel cells, organelle-based biofuel cells, and microbial fuel cells. It also discusses the different mechanisms of sensing, including utilizing the analyte being the substrate/fuel for the biocatalyst, the analyte binding the biocatalyst to the electrode surface, the analyte being an inhibitor of the biocatalyst, the analyte resulting in the blocking of the bioelectrocatalytic response, the analyte reactivating the biocatalyst, Boolean logic gates, and combining affinity-based biorecognition elements with bioelectrocatalytic power generation. The final section of this review details areas of future investigation that are needed in the field, as well as problems that still need to be addressed by the field.