Determination of the mineral surface composition and structure at molecular and atomic levels and understanding adsorption mechanisms and kinetics are crucial to perform efficient separation processes for mineral beneficiation. This understanding is a fundamental requirement to make possible the prediction and control of the macroscopic surface properties that govern the efficiency of separation technologies. 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 interface phenomena delivered by this technique are superior to other single techniques. The experiments are fast and non-destructive. High sensitivity (part of monolayer), in- situ collected information in a multiphase system even in the region of a strong absorption of substrate, makes this technique a very valuable experimental tool. The complexity of the recorded reflection spectra, their sensitivity to any 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 strength of the technique. In this paper a few examples of application of this multidiagnostic technique for monitoring surface modifications of sulphide and semisoluble minerals for selective flotation are overviewed in detail.