Depletion of high-grade resources has necessitated the use of low-grade fines, which contain good amount of mineral values and also liberate in finer sizes. Froth flotation, a physico-chemical surface-based process, is the most established solution, both technologically and economically, compared to other alternatives for fines beneficiation. For a successful and effective flotation performance, an understanding of the mineral surface and proper selection of the surfactant/reagent regimes along with their molecular chemistry and their specific adsorption mechanism are mandated. This chapter focuses on the complexity of the flotation process along with adsorption and interaction mechanism of different surfactants in accordance to mineral surface characteristics and their dependency on many microevents. To further strengthen mineral flotation chemistry and advancement of mineral engineering, research gears at investigating new surfactants, specific for particular mineral surface. The selection of reagents/surfactants with appropriate chemical composition and their administration are of critical importance in view of varied mineralogy, chemical complexity and size consist of feed material. Costeffective and lower cost flotation reagents can be synthesized through insertion of new functional groups, molecular modelling of reagents for more environmentfriendly nature, modifying the structure of other chelating agents and novel green chemicals from renewable resources, adding aliphatic alcohol and carboxylic acid to bio-based collectors and adding chaotropic anions to alkyl and aryl surfactants and organic and inorganic salts having strong orientation with more proton donor and acceptor; addition of another cationic group to known cationic surfactants can be tried for enhanced flotation performance. The study also provides an idea on the effect of other parameters like pH, composition of pulp, zeta potential, electrostatic potential, etc. For envisagement of a successful flotation performance, proper selection of the reagent system according to the specific surface and understanding of the mineral surface-specific adsorption mechanism are mandated.