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 ų, the single-cavity CB[n] hosts exhibit unique selectivity for differently sized guest molecules and ions: the CB[5] can bind small gas molecules, CB[6] binds aliphatic chains, CB[7] can include aromatic and polycyclic guests, CB[8] allows for the binding of two complementary guests, while CB[10] 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[7] result from optimal packing of the hydrophobic cavity with the guest core and the placement of an ammonium group adjacent to each portal.