A variety of assay technologies continue to be developed for high-throughput screening. These include cell-based assays, surrogate systems using microbial cells such as yeast and bacterial two-hybrid and three-hybrid systems, and systems to measure nucleic acid-protein and receptor-ligand interactions. Modifications have been developed for cell-free, homogeneous assay systems, such as time-resolved fluorescence, fluorescence polarization and the scintillation proximity assay. Innovations in engineering and chemistry have led to delivery systems for nanoliter volumes and sensitive biosensors for ultra-high-throughout screening conducted in nanoliter and picoliter volumes. Spectroscopic methods have been extended to read single molecule fluorescence. Technologies are being developed to identify new targets from genomic information in order to design the next generation of screens.