Self-assembling nanostructures in aqueous mixtures of bilayer-forming lipids and micelle-forming surfactants are relevant to in vitro studies on biological and synthetic membranes and membrane proteins. Considerable efforts are currently underway to replace conventional detergents by milder alternatives such as styrene/maleic acid (SMA) copolymers and fluorinated surfactants. However, these compounds and their nanosized assemblies remain poorly understood as regards their interactions with lipid membranes, particularly, the thermodynamics of membrane partitioning and solubilisation. Using (19)F and (31)P nuclear magnetic resonance spectroscopy, static and dynamic light scattering, and isothermal titration calorimetry, we have systematically investigated the aggregational state of a zwitterionic bilayer-forming phospholipid upon exposure to an SMA polymer with a styrene/maleic acid ratio of 3 : 1 or to a fluorinated octyl phosphocholine derivative called F(6)OPC. The lipid interactions of SMA(3 : 1) and F(6)OPC can be thermodynamically conceptualised within the framework of a three-stage model that treats bilayer vesicles, discoidal or micellar nanostructures, and the aqueous solution as distinct pseudophases. The exceptional solubilising power of SMA(3 : 1) is reflected in very low membrane-saturating and solubilising polymer/lipid molar ratios of 0.10 and 0.15, respectively. Although F(6)OPC saturates bilayers at an even lower molar ratio of 0.031, this nondetergent does not solubilise lipids even at >1000-fold molar excess, thus highlighting fundamental differences between these two types of mild membrane-mimetic systems. We rationalise these findings in terms of a new classification of surfactants based on bilayer-to-micelle transfer free energies and discuss practical implications for membrane-protein research.