Stimulants that act on the central nervous system have been used since antiquity for ritual and other uses. Organic chemistry techniques, especially those developed in Germany in the late 1800s, resulted in the isolation and structural determination of several important stimulants. Synthetic pathways for amphetamine and related stimulants were developed in the first half of the 19th century, and these new drugs were widely marketed. Awareness of abuse potential emerged soon after but was contested. Stimulants have been used to counteract fatigue and promote wakefulness during military operations, as well as to treat sleep disorders, since the 1930s. Methylphenidate was approved to treat children with behavioral problems in 1962, predating the recognition of attention deficit hyperactivity disorder (ADHD). Stimulant abuse became a political concern in the post-war period, initially with the use of “pep-pills” by long-haul truck drivers and later as drug dealing became common in night clubs, with new laws limiting availability passed in the early 1960s. They have also been used to increase athletic and cognitive performance. Stimulants are still first-line therapies for ADHD and some sleep disorders; however, newer-generation drugs have been developed with better safety profiles and lower abuse potential. Illicit stimulant use continues to be common in many countries.