The programmability of oligonucleotide recognition offers an attractive platform to direct the assembly of reactive partners that can engage in chemical reactions. Recently, significant progress has been made in both the breadth of chemical transformations and in the functional output of the reaction. Herein we summarize these recent progresses and illustrate their applications to translate oligonucleotide instructions into functional materials and novel architectures (conductive polymers, nanopatterns, novel oligonucleotide junctions); into fluorescent or bioactive molecule using cellular RNA; to interrogate secondary structures or oligonucelic acids; or a synthetic oligomer.