Catalytic RNA is increasingly viewed as a promising drug target, particularly in that some catalyze activities specific to microorganisms and viruses. On page 56, Jenne et al. describe a fluorescence-based assay to find inhibitors of such catalytic RNA. They used a high-throughput FRET-based assay that reports the activity of a hammerhead ribozyme. The ribozyme cleaves a specially designed RNA molecule holding together a fluorophore and a quencher dye, resulting in a fluorescent signal that is reduced by inhibitors of the ribozyme. They used the assay to screen a library of 96 known antibiotics, and extracts of nearly 2,000 different actinomycete strains, and detected a number of inhibitory compounds with potential antibiotic activities, one of which they validated as effective in vivo. They estimate that even without automation such an assay could analyze on the order of 500 different ribozyme reactions per day to search for new antibiotics.