High-throughput screening (HTS) is a scientific method used in drug discovery that allows researchers to quickly test millions of chemical, genetic, or pharmacological compounds using robotics, detectors, and other automated tools. The key tool is a microtiter plate containing hundreds to thousands of wells, each with a different compound. Automated systems transfer plates between stations for mixing, incubation, and analysis to generate large amounts of experimental data. Effective experimental design, quality control, and data analysis methods are needed to identify meaningful results, or "hits", from large HTS datasets. Recent advances allow screening millions of reactions much faster and with less reagent volume than before.