Identification of uncommon targets for inhibition, such as virulence factors, represents an emerging approach for combating the problem of antibiotic resistance among bacteria. Unfortunately, the lack of effective systems for the discovery and evaluation of inhibitors for such targets has considerably slowed progress. A recent article in ACS Chemical Biology, however, details the development of an in vivo based high-throughput screening strategy for identification of small molecule inhibitors of wall techoic acid biosynthesis.