Nucleic acid aptamers can be tailored to bind a wide spectrum of molecules, and therefore are natural candidates for biosensors. Until now, however, aptamer biosensing technologies have relied on indirect methods for readout of binding. In this issue, Jhaveri et al. develop an aptamer that increases fluorescence upon target binding, providing a direct readout. They design a pool of RNA aptamers with randomly incorporated fluorescent uridines, select the ones that bind to adenosine,their target molecule, and then screen for those that displayed significant increase in fluorescence upon adenosine binding as a result of a conformational change. Jhaveri et al. identify several, and go on to test their specificity and the structural requirements for their signaling function. For high-throughput sensor arrays, such molecules could potentially be incorporated into a variety of formats, such as fiber optic cables and etched microarrays (see p. 1293).