The discovery of newdrugs is a complex process. It generally startswith the identification of compounds that bind to a target or show efficacy in a simple screen.Molecules that show good affinity are called ‘‘hits.’’ The next step is to find compounds that have attractive pharmaceutical properties—for example, lowtoxicity and sufficient aqueous solubility to be orally active. Such compounds are often called ‘‘leads.’’ Traditionally, ‘‘hits’’ have been found by screening, while ‘‘leads’’ are developed from ‘‘hits’’ through chemical synthesis. Screening normally involves large numbers of compounds fromnatural products, corporate databases, or organic chemistry companies that can be examined for biological activity in high-throughput assays. Commercial systems can process millions of tests per day for enzyme targets. The best compounds are moved forward in a process aimed at modifying their chemical structure to improve potency, specificity, and in vivo activity while lowering toxicity and side effects. Synthetic methods include combinatorial chemistry and library synthesis.