DNA serves as a versatile template for few-atom silver clusters and their organized self-assembly. These clusters possess unique structural and photophysical properties that are programmed into the DNA template sequence, resulting in a rich palette of fluorophores which hold promise as chemical and biomolecular sensors, biolabels, and nanophotonic elements. Here, we review recent advances in the fundamental understanding of DNA-templated silver clusters (Ag_N-DNAs), including the role played by the silver-mediated DNA complexes which are synthetic precursors to Ag_N-DNAs, structure–property relations of Ag_N-DNAs, and the excited state dynamics leading to fluorescence in these clusters. We also summarize the current understanding of how DNA sequence selects the properties of Ag_N-DNAs and how sequence can be harnessed for informed design and for ordered multi-cluster assembly. To catalyze future research, we end with a discussion of several opportunities and challenges, both fundamental and applied, for the Ag_N-DNA research community. A comprehensive fundamental understanding of this class of metal cluster fluorophores can provide the basis for rational design and for advancement of their applications in fluorescence-based sensing, biosciences, nanophotonics, and catalysis.