This article discusses the concept of "privileged scaffolds" in the context of library design and drug discovery. Privileged scaffolds are molecular frameworks that have the potential to interact with a wide range of biological targets, making them valuable in the development of bioactive small molecules. The authors explore the challenges in creating effective compound collections and highlight the importance of privileged scaffolds in overcoming these challenges. They provide a comprehensive list of privileged scaffolds, including those derived from natural products and synthetic compounds, and discuss examples of their use in library synthesis. The review also outlines the current state of the art in privileged scaffold library synthesis, emphasizing the need for intelligent library design and effective screening methods. The authors conclude by discussing future perspectives on identifying new privileged scaffolds, suggesting that advances in technology and computational methods could lead to the discovery of new scaffolds. Overall, the article underscores the significance of privileged scaffolds in accelerating biochemical discoveries and drug development.This article discusses the concept of "privileged scaffolds" in the context of library design and drug discovery. Privileged scaffolds are molecular frameworks that have the potential to interact with a wide range of biological targets, making them valuable in the development of bioactive small molecules. The authors explore the challenges in creating effective compound collections and highlight the importance of privileged scaffolds in overcoming these challenges. They provide a comprehensive list of privileged scaffolds, including those derived from natural products and synthetic compounds, and discuss examples of their use in library synthesis. The review also outlines the current state of the art in privileged scaffold library synthesis, emphasizing the need for intelligent library design and effective screening methods. The authors conclude by discussing future perspectives on identifying new privileged scaffolds, suggesting that advances in technology and computational methods could lead to the discovery of new scaffolds. Overall, the article underscores the significance of privileged scaffolds in accelerating biochemical discoveries and drug development.