Primary amides are unique supramolecular synthons possessing two hydrogen donors and two hydrogen acceptors. By interacting in a complementary fashion, primary amides reliably generate two-dimensional hydrogen bonded networks that differ from conventional hydrogen bonded structures such as carboxylic acid dimers or one-dimensional secondary amide chains. This feature permits the design of sophisticated supramolecular assemblies based on primary amides (especially aromatic amides). Several interesting crystal structures have been constructed utilizing primary amides, although such structures have been applied only in the field of crystal engineering because the networks strongly favor crystallization. Expansion of the applications of primary amides to liquid crystals and self-assembly in solution requires an appropriate balance between primary amide-based hydrogen bonding and other noncovalent interactions. This perspective article reviews the key hydrogen bonding properties of primary amides determined from crystal structure studies, and a variety of supramolecular assemblies involving primary amides are discussed. A new strategy for overcoming crystallinity and solubility issues is proposed, involving introduction of a trifluoromethyl group at the ortho position of the aromatic primary amide. Such substitutions produce highly processable primary amides, while maintaining the two-dimensional hydrogen bonded network. Examples of self-assembly using 2-trifluoromethylbenzamide demonstrate its usefulness in self-assembly.