In biocatalysis transformation, the solvent have to fulfill a large number of requirements, such as high substrate solubility, high enzyme activity and stability, and positive effects on reaction equilibrium. In addition, and with the emergence of the green chemistry concept in the 90s, many studies aim at developing and promoting the use of “green solvents”, introducing new difficulty in the selection and panel of choice. Although many enzymatic synthesis reactions in water- or non-water environment (e.g. organic solvents, ionic or supercritical fluids) have been developed, sometimes with high efficiency, no medium meets every challenge at the same time, and therefore a need for novel solvents suited for different reaction types and applications is still in investigation. Deep eutectic solvents (DESs) have recently been tested as media in different biocatalytic processing. Their unusual and strong solvation capacities, combined with a very low toxicity, nonvolatility, nonflammabilty, and with possible biodegradability, make these solvents ideal candidates to carry out biotransformation. Several examples of biocatalysis in Deep Eutectic Solvents will be presented and a focus will be made on parameters affecting the enzymatic performance. Moreover, a description of challenges and opportunities will be discussed.