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Even \u201csimple\u201d drug association to phospholipid bilayers can only be fully understood if the slab\u2010of\u2010hydrocarbon approach is abandoned and the complex, anisotropic properties of lipid bilayers reflecting the chemical structures and organization of the constituent phospholipids are considered. The interactions of drugs with phospholipids are important in various processes, such as drug absorption, tissue distribution, and subcellular distribution. In addition, drug\u2013lipid interactions may lead to changes in lipid\u2010dependent protein activities, and further, to functional and morphological changes in cells, a prominent example being the phospholipidosis (PLD) induced by cationic amphiphilic drugs. Herein we briefly review drug\u2013lipid interactions in general and the significance of these interactions in PLD in particular. 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