To screen efficiently the millions of compounds that are synthesized using combinatorial and automated methods, dramatically improved assay technologies are currently needed. In 96-well microtiter plates, nonradioactive techniques (primarily fluorimetric) and cell-based functional methods have moved to the cutting edge, while clever assays that extract information from large bead-based combinatorial libraries have begun to show considerable promise. In the future, miniaturized assays that break out of the 96-well format will be enabled by innovative technologies for high-throughput screening.