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This chapter provides an overview of the history of disease and its treatments, from antiquity to current day. Starting from trial-and-error discoveries of natural products with pharmacological activity, humans have codified their knowledge of natural product–based therapeutics and its refinement over the centuries. During the 19 th century, chemists who isolated active ingredients from natural products heralded the start of systematic studies of the chemical basis of pharmacology. Advances in synthetic organic chemistry during this period allowed scientists to begin to create chemical analogues of the active ingredients found in natural products, beginning the systematic study of structure–activity relationships (SARs). The early 20 th century saw the development of the receptor theory of drug action, which remains today the scientific underpinning of modern pharmacology and drug discovery. The 20 th century also saw advances in many scientific disciplines that all converged to create the modern, systematic approaches used today for molecular targeted drug discovery.