Chapter 3 describes the supramolecular host–guest chemistry of unmodified cucurbit[n]urils (single-cavity CB[n], n=5–8, 10, and twisted tCB[n], n=13–15). The ranges of host–guest complexes formed with the single-cavity and twisted CB[n] hosts are surveyed, and their applications, notably in the field of drug and biomolecule recognition, are described. With inner cavity volumes ranging from 68 to 691 Å3, the single-cavity CB[n] hosts exhibit unique selectivity for differently sized guest molecules and ions: the CB can bind small gas molecules, CB binds aliphatic chains, CB can include aromatic and polycyclic guests, CB allows for the binding of two complementary guests, while CB can bind other small host molecules, as well as transition metal complexes. The host–guest complexation is driven primarily by the hydrophobic effect in terms of the release of high-energy waters from the cavity upon guest inclusion, along with favorable ion–dipole interactions between the polar portals and charged centers on cationic guests. The ultra-high stability constants (up to 1017 M−1) observed with certain dicationic guests and CB result from optimal packing of the hydrophobic cavity with the guest core and the placement of an ammonium group adjacent to each portal.