Biphasic systems based on neoteric solvents, e.g. ionic liquids (ILs), supercritical carbon dioxide (scCO₂), fluorous solvents (FSs) and liquid polymers (LPs), represent interesting alternatives to organic solvents for designing continuous clean biotransformations methods in non-aqueous environments that directly provide pure products. The classical advantages of scCO₂– its ability to extract, dissolve and transport chemicals – are complemented by the high catalytic efficiency of enzymes in liquid neoteric solvents (e.g. ILs, LPs or FSs). Enzyme behaviour in scCO₂ and ILs, as well as the phase behaviour of ILs/scCO₂, are key parameters for carrying out integral green bioprocesses in continuous operation. Experimental approaches, reactor designs and results are discussed in this Critical review.