Caffeine is the most widely consumed drug in the world and the principal pharmacological source of arousal, alertness, and wakefulness for millions of people. This chapter provides a backdrop against which to understand the science of the drug by detailing the major sources of caffeine and their social and cultural history. Caffeine occurs naturally in the leaves, seeds, or fruit of over 60 plants, including those that produce coffee beans, tea leaves, and cocoa beans. The Robusta plant is similar to Arabica in size, shape, and time to maturity, but produces smaller and rounder beans that contain nearly twice the amount of caffeine found in Arabica. It became clear that some individuals reacted with hyperarousal and anxiety even to fairly small amounts of caffeine. Significant advances in decaffeination awaited the 20th century, at which time Ludwig Roselius brought about the development of a new approach. The amount of caffeine in coffee beans ranges from 1.01 to 1.42% by weight.