A better knowledge of the molecular processes behind drug-membrane interactions is essential for the development of novel medications. To far, a number of biochemical and biophysical methods have been developed to study biological membranes at the molecular level. This review centers on the accomplishments and new uses of contemporary analytical methods, such as spectrometry, calorimetry, acoustic sensing, and chromatography, in the investigation of drug interactions with lipid membranes. The benefits and drawbacks of these approaches were compared and carefully considered. Moreover, several biomimetic model membrane types, including lipid monolayers, liposomes, and supported lipid monolayers/bilayers, were described. Additionally, a brief overview of the general mechanics underlying the drug-membrane interaction process was given.