The predictability of nucleic acid hybridization offers an attractive platform to program the assembly of tagged ligands or reactants. Hybridization can be used to display multiple ligands in order to gain affinity and/or selectivity through the cooperative interaction of each ligand. Additionally, hybridization of tagged reagents increases their effective concentration and accelerates reactions. In both cases, an oligonucleotide directs an assembly to yield a functional output in the form of enhanced binding, inhibition, or reaction; for example, a reaction can be used to unmask a fluorophore or a bioactive molecule. This review provides an account of our research in this area as well as future directions.