Determination of the adsorbed layer composition and structure at molecular and atomic levels and understanding adsorption mechanisms and dynamics are vitally important for the preparation of surface layers with specific functions. Direct information, at a molecular level, about mineral surface composition, its structure and surface distribution is crucial to perform an efficient separation process for mineral beneficiation. This information is equally important for modifying surface properties of industrial minerals for specific applications such as: fillers, composites, weathering resistance, etc. An understanding of the mechanisms and kinetics of the interaction of first adsorbed organic molecules with mineral surfaces is a fundamental requirement for the prediction and control of the macroscopic surface properties governing the efficiency of separation technologies or new material formulations. The developed infrared external reflection technique has a unique ability to study interface phenomena, at a molecular level, on heterogeneous substrates. The variety, precision and reliability of information about the interface phenomena delivered by this technique is superior to any other single technique. The experiments are fast and non-destructive. High sensitivity (starting from 20 per cent of the monolayer) in situ collected information in a multiphase system, even in the region of strong absorption of the substrate, makes this technique a very valuable experimental tool. The complexity of the recorded reflection spectra, their sensitivity to variations of the optical properties of all bulk and surface components and their spatial distribution in the system under investigation, are in fact the major strengths of this technique. A few examples of the application of this multi-diagnostic technique, for monitoring surface modifications of semi-soluble minerals for selective flotation, will be discussed in detail in this paper.