Foldamers offer a unique avenue to study reactivity and can be utilized as highly efficient catalysts to accomplish difficult macrocyclizations. Foldamer catalysts offer several features key to unlocking novel reactivity. Foldamers can be rationally designed, guided by the extensive crystallographic and solution state data available. The polyamide backbone is highly modular and chiral, allowing for facile incorporation of catalytic groups for enantioselective reactions in the future. One could even imagine catalysts bearing more than two catalytic groups, particularly with diads displayed from opposing faces of the helix. Because they allow rational control of reactive group geometry, foldamer scaffolds can be seen as complementary to widely studied small molecule scaffolds for the development of new and diverse catalytic activities.