AbstractStability is one of the most important properties of drug candidates. Instable compounds can lead to false positive high‐throughput screening (HTS) hits, incorrect bioassay results, erroneous structure–activity relationships (SAR), low oral bioavailability, drug withdrawal, toxic reactions from degradation products, and difficult formulation development. Screening of stability has been implemented early in drug discovery to identify labile chemotypes and guide structural modification. The most commonly applied stability studies in drug discovery are stability–pH profile, stability in gastrointestinal fluids, stability in bioassay media, excipient compatibility, and prodrug screening. The strategy enhances the quality of drug development candidates and reduces the risks.