A complex or association between two molecules is described as host-guest when one is much larger than the other. The large host is often a macrocyclic molecule or other macromolecular structure. The guest may be anything from a single metal ion to another (smaller) macromolecule. This is a very common situation in biochemistry, where enzymes (with very large molecular weights) bind small ligands (guests) as their substrate.

For example, crown ethers bind metal ions in the central space of the ring. The liganding oxygen atoms form bonds with the metal and the whole host molecule shields the metal from the solvent. Other host-guest interactions are mediated by hydrophobic forces or hydrogen bonds , such as cyclodextrins binding steroids.

The large size of some cavities in hosts means that many different guests can fit. However, many have been designed or functionalised to be specific for certain molecules. This has lead to possible applications for host-guest chemistry in the field of molecular sensors and catalytic mimics. Indeed, some enzyme active sites have been modelled with much simpler small(er) molecule chemistry that preserves the geometry of the site but not the scaffold.