Fragment-based drug discovery (FBDD) has grown and matured to a point where it is valuable to keep track of its extent and details of application. This Perspective summarizes successful fragment-to-lead stories published in 2019. It is the fifth in a series that started with literature published in 2015. The analysis of screening methods, optimization strategies, and molecular properties of hits and leads are presented in the hope of informing best practices for FBDD. Moreover, FBDD is constantly evolving, and the latest technologies and emerging trends are summarized. These include covalent FBDD, FBDD for the stabilization of proteins or protein-protein interactions, FBDD for enzyme activators, new screening technologies, and advances in library design and chemical synthesis.