We report a strategy for the reagentless transduction of DNA hybridization into a readily detectable electrochemical signal by means of a conformational change analogous to the optical molecular beacon approach. The strategy involves an electroactive, ferrocene-tagged DNA stem-loop structure that self-assembles onto a gold electrode by means of facile gold-thiol chemistry. Hybridization induces a large conformational change in this surface-confined DNA structure, which in turn significantly alters the electron-transfer tunneling distance between the electrode and the redoxable label. The resulting change in electron transfer efficiency is readily measured by cyclic voltammetry at target DNA concentrations as low as 10 pM. In contrast to existing optical approaches, an electrochemical DNA (E-DNA) sensor built on this strategy can detect femtomoles of target DNA without employing cumbersome and expensive optics, light sources, or photodetectors. In contrast to previously reported electrochemical approaches, the E-DNA sensor achieves this impressive sensitivity without the use of exogenous reagents and without sacrificing selectivity or reusability. The E-DNA sensor thus offers the promise of convenient, reusable detection of picomolar DNA.