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Since its concept was conceived in 1992, DNA-encoded libraries (DELs) have evolved into a valuable technology for hit identification in drug discovery. The DEL technology enables the fast and economic synthesis, screening, and analysis of DNA-encoded collections of millions to trillions of compounds against biological targets through a confluence of molecular biology, combinatorial chemistry, high throughput sequencing and advanced informatics techniques. This whitepaper will provide the drug discovery community with a better understanding of DEL technology and stimulate innovation in the field by describing the DEL design, synthesis, screening and expanded applications.