Leading investigators review the highlights of current fibrosis research and the experimental methodologies used uncover the mechanisms that drive it. In their discussion of research methodologies utilizing cultured cells to model various aspects of the fibrotic response in vitro, the authors describe the isolation, characterization, and propagation of mesenchymal cells, and highlight the similarities and differences between methods that are appropriate for different types of fibroblasts. Approaches for studying collagen gene regulation and TGF-b production are also discussed, along with experimental methodologies utilizing animal models to study the pathogenesis of fibrosis. The protocols follow the successful Methods in Molecular MedicineTM series format, each offering step-by-step laboratory instructions, an introduction outlining the principles behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.