Though it has been synthesized in the lab, quinine occurs naturally in the bark of the cinchona tree. The medicinal properties of the cinchona tree were originally discovered by the Quechua Indians of Peru and Bolivia; later, the Jesuits were the first to bring the cinchona to Europe.

Quinine was the first effective treatment for malaria caused by Plasmodium falciparum, appearing in therapeutics in the 17th century. It remained the antimalarial drug of choice until the 1940s, when other drugs replaced it. Since then, many effective antimalarials have been introduced, although quinine is still used to treat the disease in certain critical situations, i.e., as in impoverished regions. Quinine is available with a prescription in the United States and over-the-counter, in very small quantities, in tonic water. Quinine is also used to treat lupus and arthritis. Quinine was also frequently prescribed in the U.S. as an "off-label" treatment for nocturnal leg cramps, but this has since been prohibited, in effect, by an FDA statement warning against the practice.

Quinine is very sensitive to ultraviolet light (UV) and will fluoresce in direct sunlight, due to its highly conjugated resonance structure (see Quinoline).