Lipophilic compounds are of significant importance in modern biotechnology. Centerly of interest are the biodegradation as well as the biotransformation of such lipophilic and often water-immiscible substances. Both whole cells and/or enzymes are used for these processes. It is obvious that a wide range of problems arise in an application of such complex systems consisting of biocatalysts substrate(s), product(s), water, (in some cases water-immiscible organic solvents): (i) interactions between lipophilic compounds and the membranes resulting in the change of some physiological characteristics of the living system; (ii) problems in the transport of these compounds (substrates and/or products) within the complex structured reaction systems; (iii) the problem of increasing the solubility of the lipophilic and mostly water-immiscible compounds with a minimum of inhibition effects on the processes; (iv) the presence of lipophilic components may also cause changes of the transport processes within the system (e.g. immobilized cells) resulting in changed yield or activity of the biological system. These problems are critically discussed in this review in relation to the known modes of interaction of lipophilic compounds with membranes, the bioavailability of the substrates, and the cases of steroid biotransformations. An outlook of future aspects in research, development and application of such processes is given.