The stability of colloidal suspensions is determined primarily by the interactions among suspended particles, which in turn depends on pH, electrolyte concentration, temperature and so on. In most practical systems, flocculation or stabilization is controlled by adsorbing polymers, surfactants or their mixtures. In this paper, the role of adsorbed layer microstructural properties, particularly polymer conformation at solid-liquid interface, in controlling stability and efficiency of flocculation is examined. When polymers are used, their conformation can be manipulated by changing solution conditions such as pH and/or by the addition of a secondary polymer or surfactant. A multi-pronged approach involving the use of fluorescence, ESR, Raman and NMR spectroscopic techniques along with measurements of surface charge and hydrophobicity was employed to explore the structure of the adsorbed layer. A detailed population balance model for coagulation and flocculation of colloidal suspensions by inorganic salts and polymers is then presented incorporating the modern theories of surface forces. In particular, the classical DLVO theory is modified for flocculation by polymers and integrated in a population balance framework for the kinetics of flocculation. The open and irregular structure of floes is accounted for by embedding the mass fractal dimension of flocs in the model. For demonstration, the evolution of mean floc size with time is simulated for flocculation of hematite and polystyrene latex suspensions. The model predictions are in reasonable agreement with experimental data. As it is computationally less intensive, the proposed model can be utilized for online optimization and control of solid-liquid separation processes that are widely encountered in water treatment, mineral processing, waste management, and so on.