We show that the theory of the surface energy of condensed phases, which is based on its separation into London–van der Waals and acid–base components, can be used for the interpretation of adhesion force and work of adhesion measurements with the chemical force microscope. However, it can be done in a straightforward manner only for surfaces and liquids with the same type of solvation. Even in this case, some complicating factors like dissimilarity of the interacting hydro- and fluorocarbon groups has to be considered. At lyophilic surfaces liquid tends to form layered solvation structures at the interface and the presence of these structures may influence interfacial energies. We show that this type of effect can be very significant for hydrophilic surfaces in water. For instance, we found the surface free energy of the OH or COOH terminated monolayers in water is 20÷40 mJ m −2 higher than interfacial energy in hexadecane. Additionally, we predict that if liquid forms a layered structure at the interface, the observed adhesion force depends on the load applied to the CFM cantilever. The experimental evidence of such a behavior is presented.