In this review, the possible role of membranes on drug transport, distribution, accumulation, efficacy, and resistance is discussed.

The interest in drug development, research, and QSAR is especially focused on the interaction of ligand (drug) molecules and the proteins of the specific receptor. It is widely assumed that the biological activity of drugs (such as tranquilizers, anesthetics, β-blockers, antidepressants, etc.) arises as a result of binding to active sites in membrane-bound proteins, whereas the lipid background is considered to play a more passive role. In the last decade, however, evidence is increasing that we may have underestimated the influence of drug-membrane interactions on drug action. These membranes do not consist of lipids only but possess polarized phosphate groups and neutral, positively or negatively charged head groups, and are highly structured and chiral. The consequences of drug-membrane interaction on transport, distribution, accumulation, efficacy, and resistance cannot always be explained sufficiently by mere partitioning processes, i.e., by log Poctanol/water.