The energy of interaction of particles with dissimilar wettability (quartz, coal, and pyrite) and air bubbles in neutral and alkaline media are analyzed on the basis of the extended DLVO theory to assess the floatability of these minerals. It is established that for hydrophilic materials such as quartz, the formation of particle-bubble complexes (at both the primary, and also secondary potential minima) is impossible owing to existence of a high potential barrier and weak force of attraction. For coal and pyrite, the pattern of the potential curves (energy of interaction versus distance between particle and bubble) will depend largely on the pH of the medium: an increase in this parameter will lead to manifestation of a potential barrier (when pH ≈ 7.8 for coal, and pH ≈ 9.8 for pyrite), and to an increase in its height. This causes unstable flotation of the coal and pyrite even for relatively small changes in the surface potential, pH, and ionic composition of the medium. An increase in the effectiveness of flotation benefication of coal and pyrite can be achieved by hydrophobization of the minerals by reagents-collectors: the wetting angle is increased from 50–80° to 90–100°. In turn, the potential barrier is eliminated, the effect of the pH of the medium is neutralized, and stable attachment of particles of the minerals under consideration to air bubbles is ensured in the region of the secondary potential minimum. Analysis of the forces of particle-bubble interaction made it possible to determine the forces of adhesion and detachment. Computed values of the forces in question for an air-bubble/hydrophobized-pyrite-particles system are comparable to experimental values of the indicated forces for a similar system.