The predictable nature of nucleic acid hybridization offers a simple platform to program assemblies with emerging function. This review will highlight some examples from our laboratory towards the use of this concept in chemical biology. These developments capitalize on peptide nucleic acids (PNAs), a functional analogue of natural oligonucleotides to program assemblies. In the first example, hybridization is used to organize mixtures of molecules tagged with PNAs into a microarray format; in the second example, the PNA tags are used to program the dimerization of ligands onto a nucleic acid template which translates into enhanced affinity for a biomolecule; in the third one, hybridization is used to program a reaction by aligning reactive functional groups and translated into a fluorescent signal. While these examples are only a prelude in translating instructions into a function, we hope that they can be the basis of more complex network and inspire further developments in the broader context of system chemistry.