This book explains the ligand-binding theory and practice using it as a lens for understanding the thermodynamic and molecular basis for macromolecular structure, function, and stability, and for introducing the strengths, weaknesses, and complementarities among major contemporary methods that are used in experimental analysis of macromolecular properties. It develops general guidelines that aid in designing and evaluating experiments where ligand binding is probed. Further, it explains the relationships that govern simple and complex molecular interactions, yet, maintains a firm grounding in chemical principles and invoking minimum mathematical formalism.