Fragment-based lead discovery has over the years matured into an attractive alternative to high-throughput screening (HTS) for lead generation. Several techniques for screening libraries of typically 10(3)-10(4) fragments have been reported. In this work, the practical success rates that can be expected from the screening of fragment-like libraries was investigated via interrogating medicinal chemistry databases for several programs with virtual libraries created from commercially available reagents or with libraries of commercially available fragments. The results suggest that hits more potent than typically discovered in today's fragment-based screens can consistently be identified from realistically accessible compound sets under screening conditions similar to commonly used HTS protocols.