This feature article is an overview of the recent research activity in the area of enzyme-based biofuel cells implanted and operating in vivo in living creatures (insects, mollusks, rats, rabbits, etc.). The electrical power extracted from these biological sources presents use for activating microelectronic devices for biomedical applications (e.g. pacemakers) or sensors/biosensors for environmental monitoring. The inequality of the voltage generated by the biofuel cell (which is thermodynamically limited by the redox potentials of the biomolecular fuel and oxygen) and the voltage demanded by the electronic devices requires special attention and can be resolved by specific interfacing with charge pumps and DC–DC converters. The paper focuses on the problems in the present technology as well as offers their potential solutions. Lastly, perspectives and future applications of the implanted biofuel cells are also discussed.