The review demonstrates the recent theoretical and experimental progress in the understanding of penetration systems at the air–water interface in shich a dissolved amphiphile (surfactant, protein) penetrates into a Langmuir monolayer. The critical review of the existing theoretical models which describe the thermodynamics of the penetration are critically reviewed. Although a rigorous thermodynamic analysis of penetration systems is unavailable due to their complexity, some model assumptions, e.g. the invariability of the activity coefficient of the insoluble component of the monolayer during the penetration of the soluble component result in reasonable solutions. New theoretical models describing the equilibrium behaviour of the insoluble monolayers which undergo the 2D aggregation in the monolayer, and the equations of state and adsorption isotherms which assume the existence of multiple states (conformations) of a protein molecule within the monolayer and the non-ideality of the adsorbed monolayers are now available. The theories which describe the penetration of a soluble surfactant into the main phases of Langmuir monolayers were presented first for the case of the mixture of the moleucles possessing equal partial molar surfaces (the mixture of homologues), with further extension of the models to include the interesting process of the protein penetration into the monolayer of 2D aggregating phospholipid. This extension was based on a concept which subdivides the protein molecules into independent fragments with areas equal to those of phospholipid molecule. Various mechanisms for the effect of the soluble surfactant on the aggregation of the insoluble component were considered in the theoretical models: (i) no effect on the aggregate formation process; (ii) formation of mixed aggregates; and (iii) the influence on the aggregating process via the change of aggregation constant, but without any formation of mixed aggregates. Accordingly depending on the mechanism, different forms of the equations of state of the monolayer and of the adsorption isotherms of soluble surfactant are predicted. Based on the shape of the experimental Π-A isotherms, interesting conclusions can be drawn on the real mechanism. First experimental evidence has been provided that the penetration of different proteins and surfactants into a DPPC monolayer in a fluid-like state induces a first order main phase transition of pure DPPC. The phase transition is indicated by a break point in the Π(t) penetration kinetics curves and the domain formation by BAM. Mixed aggregates of protein with phospholipid are not formed. These results agree satisfactorily with the predictions of the theoretical models. New information on phase transition and phase properties of Langmuir monolayers penetrated by soluble amphiphiles are obtained by coupling of the Π(t) penetration kinetics curves with BAM and GIXD measurements. The GIXD results on the penetration of β-lactoglobulin into DPPC monolayers have shown that protein penetration occurs without any specific interactions with the DPPC molecules and the condensed phase consists only of DPPC.