Optical reagentless biosensors are one of the most promising alternatives for producing selective, sensitive and autonomous sensors for real life applications. These devices are based on the efficient use of the spectroscopic properties of bioreagents, mainly proteins, as transducers; avoiding in this way the use of chemical colorant/fluorophores which usually limit sensors performance. In this paper a brief state of the art of the bioreagents being used in biosensors as well as recent alternatives are discussed. The advantages of flavoenzymes and hemeproteins as the basis for reagentless biosensors are particularly stressed.