The common principles of molecular recognition with cooperative or bidentate hydrogen bonds, dispersion forces and hydrophobic packing govern the specificity of protein-carbohydrate interaction. Enthalpy/entropy-compensation is also valid, maintaining KD-values in the range of 30 mM to 200 nM. The individual contributions of the enthalpic and entropic factors which originate from the receptor, the ligand and/or the solvent to the overall free energy change can at least be estimated by a combination of computer-assisted molecular modeling, NMR spectroscopy of the reactants before and after complex formation and thermodynamic measurements. The delineation of adaptable parameters such as ligand or receptor side chain flexibility points to a route to practicable guidelines for a rational design of mimetics in glycosciences.