Various issues that surround biocatalysis in ionic liquids are reviewed and presented in details. The effects of ionic liquids (ILs) on the structure and activity of enzymes as well as their thermal and operational stability is surveyed. Included also in the review is the effects of ILs on the (enantio)selectivity of biocatalytic transformations in comparison with conventional reaction media and the design of efficient reaction procedures based on its unconventional solvent characteristics. The study showed that there is hardly an IL that is not tolerated by any enzyme, and the impression is generally tolerated to higher concentrations than water-miscible molecular solvents. Ionic liquids have potential as reaction media for biotransformation of highly polar substrates, such as polysaccharides, which cannot be performed in water, owing to equilibrium limitations. It is expected that green and biocompatible ionic liquids will become available to contribute to a greener chemical industry.