To generate the desired effect in the human body, the active pharmaceutical ingredient usually needs to interact with a receptor located on the cell membrane or inside the cell. Thus, understanding membrane interactions is of great importance when it comes to the development and testing of new drug molecules or new drug delivery systems. Nowadays, there is a tremendous selection of both model cell membranes and of techniques that can be used to characterize interactions between selected model cell membranes and a drug molecule, an excipient, or a drug delivery system. Having such a wide selection of model cell membranes and techniques available makes it sometimes challenging to select the optimal combination for a specific study. Furthermore, it is difficult to compare results obtained using different model cell membranes and techniques, and not all in vitro studies translate as well to an estimation of the in vivo biological activity or understanding of mode of action. This review provides an overview of the available lipid bilayer-based model cell membranes and of the most widely employed techniques for studying membrane interactions. Finally, the need for employing complimentary characterization techniques in order to acquire more reliable and in-depth information is highlighted. (C) 2020 Published by Elsevier B.V.