Quantitative chemical and physical insight enable rational, design-oriented approaches to the early phases of drug discovery. High-resolution biophysical and biochemical measurements provide detailed mechanistic, kinetic, and structural information on compound-target interactions. They may reveal binding kinetics, identify challenging targets associated with protein-protein interactions, and provide the foundation for fragment-based drug discovery. These techniques yield information on aggregation, solubility, and cell permeability and accelerate hit-to-lead drug discovery, prioritization, and optimization.