Cyclodextrins are cyclic oligosaccharides obtained by enzymatic degradation of starch. They are remarkable macrocyclic molecules that have led major theoretical and practical advances in chemistry, biology, biochemistry, health science, and agriculture. Their molecular structure is composed of a hydrophobic cavity that can encapsulate other substances to form inclusion complexes through host-guest interactions. This unique feature is at the origin of many applications. Cyclodextrins and their derivatives have a wide variety of practical applications in almost all sectors of the industry, including pharmacy, medicine, foods, cosmetics, chromatography, catalysis, biotechnology, and the textile industry. Villiers published the first reference to cyclodextrins in 1891. Since the beginning of the twentieth century, major researchers, such as Schardinger, Pringsheim, Karrer, Freudenberg, French, Cramer, Casu, Bender, Saenger, Nagai, Szejtli, and Pitha, have paved the history of the cyclodextrins. Several time periods have marked their history. After their discovery and characterization from 1891 to 1911, there has been a period of doubt and disagreement from 1911 to 1935. Then, the 1935–1950 exploration period was marked by structural results on the “Schardinger dextrins.” In 1949, Cramer introduced the cyclodextrin-based nomenclature. Research between 1950 and 1970, the period of maturation, focused on conformations and spectroscopic data of cyclodextrins and their inclusion complexes, with applications in catalysis and as enzyme models. Finally, the period of use has been ongoing since 1970 and has seen cyclodextrins find many industrial applications. Cyclodextrins have then found many industrial applications, initially in the pharmaceutical and food sectors. In 1984, the first chromatographic columns were commercialized. At that time, many cyclodextrin-based catalysts were developed for biomimetic chemistry and other applications such as artificial enzymes. Currently, more than 2000 publications on cyclodextrins are published each year. In this chapter, we present a historical overview of the discovery, development, and applications of cyclodextrins.