Bioadhesion, and more specifically mucoadhesion, is becoming an important strategy for drug delivery. As a result, it is important to understand the various mechanisms that govern attachment of polymeric substances to the glycoproteins on epithelial surfaces, along with the associated structure-activity relationships of the polymer. This article reviews fundamentals of mucoadhesion, with special emphasis on structural features of the polymer as they contribute to the process of mucoadhesion. There are four possible general interactions between mucoadhesive polymers and glycoproteins: (1) covalent attachment; (2) electrostatic interaction, which requires matching of charge groups between the polymer and mucus; (3) hydrogen bonding; and (4) hydrophobic interactions. Aside from covalent attachment, which is not presently a prominent mechanism for mucoadhesion, the remaining mechanisms require maximum contact between the polymer and mucin for optimum adhesion. With polyelectrolyte polymers, the charged groups are important in controlling the degree of hydration of both the polymer and the mucous network. The expanded nature of the swollen polymer and mucus enhances the interdiffusion process and permits both a mechanical entanglement and an increase in surface contact for hydrogen bonding and/or electrostatic interaction between the polymer and the mucous network. A number of techniques are available to study mucoadhesion. Some of these are better suited to study the kinetics of the mucoadhesion process whereas others are more useful for equilibrium studies. To date, the major deficiency in basic studies of mucoadhesion is the lack of suitable information on the organization and physicochemical properties of the mucin layer.