Using single-molecule fluorescence resonance energy transfer (smFRET), Kim et al. (p 763) demonstrate that the 8-17 DNAzyme, one of the newest members of the metalloenzyme family, uses both induced fit and lock-and-key modes of catalysis, much like its proteinaceous relatives (see also News and Views by Schlosser and Li, p 753). Shown is an smFRET image beneath a schematic representation of DNAzyme catalysis, with the 8-17 DNAzyme strand in blue and the substrate in red(labeled with a FRET donor in yellow and acceptor in orange). The path on the left demonstrates global folding that occurs prior to cleavage and release of the product. The path on the right depicts binding to a prearranged DNA structure. Cover art by Erin Boyle, based on imagery provided by Alex D. Jerez, Hee-Kyung Kim and Yi Lu.