The use of water-immiscible organic solvents in whole-cell biocatalysis has been exploited for biotransformations involving sparingly water-soluble or toxic compounds. These systems can overcome the problem of low productivity levels in conventional media due to poor substrate solubility, integrate bioconversion and product recovery in a single reactor, and shift chemical equilibria enhancing yields and selectivities; nevertheless, the selection of a solvent combining adequate physicochemical properties with biocompatibility is a difficult task. The cell membrane seems to be the primary target of solvent action and the modification of its characteristics the more relevant cellular adaptation mechanism to organic solvent-caused stress. Correlations between the cellular tonicity or the extractive capacities of different solvents and some of their physical properties have-been proposed in order to minimize preliminary, solvent-selection experimental work but also to help in the understanding of the molecular mechanisms of toxicity and extraction. The use of whole cells in organic-media biocatalysis provides a way to regenerate cofactors and carry out bioconversions or fermentations requiring multi-step metabolic pathways; some processes already are commercially exploited;Immobilization can further protect cells from solvent toxicity, and has thus been effectively used in organic solvent-based systems. Several examples of extractive fermentations and other whole-cell bioconversions in organic media are presented.