A review is presented focusing on the research that combines enzymes with supercritical fluids, fluorous solvents, and under solvent-free conditions. Supercritical carbon dioxide tends to be the SCF of choice for biocatalysis because of its cheapness, availability, and the most "green" with suitable critical parameters that are compatible with conditions required for enzymatic reactions. However, CO2 is involved in two chemical processes that have the potential to reduce or destroy the catalytic activity of an enzyme. These are the formation of carbamates and the formation of carbonic acid. Secondly, biocatalysis in fluorous solvents used in conjunction with fluorous biphasic system (FBS) is an attractive research for biochemistry. Facile separations of biocatalyst from product provide cost- and time-effective processes plus it is easily reused and recycle. Lastly, biocatalysis in solvent-free conditions exhibit unusual kinetics due to lack of monomer availability and entanglement of the catalyst in the polymer during late stages of the reactions. Of more relevance is the study on heterogeneous systems involving undissolved substrates. The potential advantage for this solid state biocatalysis are the requirements for smaller reactor volumes and associated cost savings. It also provide a useful role in dissipating heat in an exothermic reaction.