This review deals with interactions at interfaces between lipases and low molecular weight amphiphiles, such as polar lipids and synthetic surfactants. The interaction between polar lipids and lipases is particularly important in the gastrointestinal tract, where fat is digested by gastric lipases in the stomach and by pancreatic lipases in the duodenum. Polar lipids have been found to influence lipase activity in numerous ways. For example, it has been found that Sn-2 monoacylglycerols, which are the main degradation products from fat metabolism, take over at the triacylglycerol oil–water interface and prevent further access of the lipase to its substrate, i.e., triacylglycerols and diacylglycerols. Additionally, different types of surfactants interact differently with lipases and the interaction can result in loss of enzymatic activity. As both lipases and the surfactants are strongly surface active, this type of interaction preferentially takes place at an interface. Lipase-surfactant interactions have been systematically studied at the air–water, the solid–water, and the oil–water interfaces. In general, it is found that cationic surfactants interact stronger than anionic or nonionic surfactants at all interfaces but not in bulk water. However, somewhat contradictory results have been reported in the literature and it is likely that the inconsistency is due to the fact that lipases of different origins are used in the different studies.