RNA- and DNA-mediation or templating of materials has been used to synthesize nanometer scale wires, and CdS nanoparticles. However, RNA and DNA have the potential to act as catalysts, which could be valuable tools in the search for new routes to materials synthesis. RNA has the ability to catalyze splicing and cutting of other RNA molecules. Catalytic activity has been extended to more general classes of reactions for both RNA and DNA using in vitro selection methods. However, catalytic activity in materials synthesis is a more recent idea that has not yet found great application. The first example of RNA-mediated evolutionary materials synthesis is discussed with specific data examples that show incompatibility of reagents in the solvent system utilized. The hydrophobic reagent Pd2(DBA)3, used as a metal precursor, was observed to spontaneously form nanostructures composed of Pd2(DBA)3 or Pd(DBA)3 rather than palladium nanoparticles, as originally reported 1. A case study of this materials synthesis example is described including the complimentary use of multi-length scale techniques including transmission electron microscopy (TEM), selected area electron diffraction (SAED), scanning TEM (STEM), electron energy loss spectroscopy (EELS), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and optical microscopy (OM). This example raises important questions regarding the extent to which non-aqueous solvents should be used in nucleic acid-mediated processes, the nature of selections in enzyme and materials development, and the requirement for chemical compatibility of the precursor molecules. The importance of good characterization tools at every stage of an in vitro selection is illustrated with concrete examples given. In order to look at the way forward for nucleic acid-mediated materials synthesis, an examination of the chemical interaction of nucleic acids with various precursors is considered. Application of density functional theory calculations provides one means to predict reactivity and compatibility. The repertoire of chemical interactions in the nucleic acids is considered vis-à-vis common metals and metal chalcogenides. The case is made for the need for water-soluble syntheses and well-controlled kinetics in order to achieve the control that is theoretically possible using nucleic-acids as a synthetic tool.