Over the last decades, high-throughput screening (HTS) of small molecule libraries has developed into a very powerful tool for drug discovery. Although HTS capabilities initially were developed almost exclusively in the domain of pharmaceutical and biotech commercial ventures, they have more recently become available in academia. The Molecular Library Initiative of the National Institutes of Health (NIH) is one example that HTS has established itself as a routine technology in biomedical research [1].

The popularity of HTS is due to rapid developments in four different areas:

1. Robotic systems. Once exotic and expensive, robotic systems and automatic liquid handling have become more affordable and easier to operate. Turnkey systems are available for the most common applications.

2. Chemical libraries. Chemical libraries are becoming more readily available and affordable to the scientific community in academia and industry. Even large compound libraries, such as the one developed for the above-mentioned Molecular Library Initiative, are accessible to the general scientific community.

3. Plate reader platforms. Reader platforms have undergone rapid development over the last two decades. As of today, high-speed microplate readers are available to very rapidly scan microplates in the 96-, 384-, and 1536-well formats or even higher densities. Automated confocal and conventional microscopes and other image-based reader platforms have evolved at an astonishing speed. Sophisticated image-based readers and corresponding image recognition and analysis software have led to the development of complex, high-content cell-based assays.

4. Detection technologies. A whole array of luminescence-based technologies have been developed and commercialized over the last few years. Among those are fluorescent proteins, high-yield fluorochromes, and luminescence substrates.