Adhesion to hydroxyapatite (which is the structural prototype of bone or tooth mineral) is a first step towards the efficacious application of restorative composites and bone cements to teeth and bones. The key medium to effect chemical adhesion between the mineralized substrate and a composite resin is a coupling agent. On the basis of many adsorption studies, primarily by the author, which are reviewed in this paper, it is proposed that a potential coupling agent suitable for dental adhesion can develop strong and durable bonds with a substrate through its hydrogen-bonding functional groups. The coupling agents must also be polyfunctional or possess some hydrophobic moieties to be hydrolytically stable. The criterion defining the capability for adhesion of a compound to hydroxyapatite is determined through a study of its adsorption characteristics from a particular solvent. The stability of this bond in aqueous environments may be determined by desorbing the adsorbed compound with water. The surface orientation of a coupling agent and whether it is reversibly or irreversibly adsorbed from a solvent primarily depend on the balance between the type, location, and number of hydrophilic and hydrophobic moieties in the agent molecule. In the case of water-soluble ionic compounds as coupling agents, the uptake of the compounds will also be influenced by the concentrations of calcium, phosphate, and hydrogen ions in the solution.