Book excerpt: This volume provides a collection of contemporary perspectives on using activity-based protein profiling (ABPP) for biological discoveries in protein science, microbiology, and immunology. A common theme throughout is the special utility of ABPP to interrogate protein function and small-molecule interactions on a global scale in native biological systems. Each chapter showcases distinct advantages of ABPP applied to diverse protein classes and biological systems. As such, the book offers readers valuable insights into the basic principles of ABPP technology and how to apply this approach to biological questions ranging from the study of post-translational modifications to targeting bacterial effectors in host-pathogen interactions.