Organosilicon compounds are ubiquitous in everyday use. Application of some of these compounds in food, cosmetics and pharmaceuticals is widespread on the assumption that these materials are not systemically absorbed. Here the interactions of various organosilicon compounds (simeticone, hexamethyldisilazane and polydimethylsiloxane) with cell membranes and models thereof were characterized with a range of analytical techniques, demonstrating that these compounds were retained in or on the cell membrane. The increasing application of organosilicon compounds as replacement of other plastics calls for a better awareness and understanding of these interactions. Moreover, with many developments in biotechnology relying on organosilicon materials, it becomes important to scrutinize the potential effect that silicone leaching may have on biological systems.