Once thought to act primarily as a storage molecule for genetic information, it is now known that DNA and RNA can have many other functions [1]. Our group is particularly interested in the ability of nucleic acids to act as catalysts. It is not yet possible to design nucleic acid sequences with catalytic activity. However, using powerful methods of artificial evolution, rare molecules that catalyze a desired reaction can be isolated from random sequence libraries of 1015 (or more) sequences. We are inspired by the power of artificial evolution, and are using this technique to learn more about the interesting and useful things that nucleic acids can do. In this presentation I will describe methods recently developed in the group to explore sequence space using secondary structure libraries (libraries enriched for a secondary structure of interest) and single-step selections (selections that can be performed in a single round rather than the ten or more that are often required). In one example of this approach, RNA-cleaving deoxyribozymes were isolated from a structured library containing a randomized region of only 12 nucleotides (corresponding to 107 different sequences) in a single round of selection followed by high-throughput sequencing [2]. In another example, a novel synthetic method [3] was used to construct a library enriched for sequences with the potential to form the secondary structure of Supernova [4], a light-producing deoxyribozyme recently discovered in our group. Active variants were isolated from this library using single-step selections, including some with improved catalytic efficiencies. These examples highlight how structured libraries can be used in combination with single-step selections to rapidly obtain information about functional nucleic acid motifs.