This chapter focuses on the intermolecular forces that govern membrane-solute interactions, the role of these forces in macromolecular adsorption, and the effects of this adsorption on membrane transport. It examines the phenomena of particle deposition and its effects on the filtrate flux. The chapter considers the effects of membrane fouling on the overall process economics, including different strategies used to control membrane fouling in different systems. The effects of protein adsorption on membrane transport depend on the relative size of the protein and membrane pores. The chapter discusses adsorption to microfiltration membranes with pores that are much larger than the size of the proteins, adsorption to semipermeable ultrafiltration membranes with pores that are comparable in size to the proteins of interest, and adsorption to fully retentive membranes that have pores that are considerably smaller than the proteins. The intermolecular interactions between the membrane solid and the various feed components are conveniently classified as being quantum mechanical, electrostatic, or polarization forces.