An overview of small-molecule screening, as carried out at the Harvard Institute of Chemistry and Cell Biology. Small-molecule libraries are prepared by split-pool synthesis on large polystyrene synthesis beads. The beads are then arrayed, one per well, into 384-well plates. Following cleavage from the beads, the compounds are resuspended in solvent and transferred into empty 384-well plates to yield stock solutions. At this point, minute amounts of the compounds can either be introduced robotically into microtiter plate assays or printed robotically onto chemically derivatized glass slides to produce small-molecule microarrays.