A brief history of natural indigo will show its extraordinary importance and explain why chemists dedicated themselves to the structural elucidation and synthesis of this pigment. Since prehistoric and ancient times, people around the world have discovered that a blue pigment can be obtained from some plants, belonging to different plant families. This pigment was suitable for both vat dyeing of textiles and for paintings. Although a large number of synthetic dyes were already available on the market in the 1870s, no synthetic substitute for indigo existed that could compete with the natural product. Between 1878 and 1882, Baeyer succeeded in establishing three routes for Indigo synthesis, using different starting materials such as isatin, cinnamic acid and o-nitrobenzaldehyde. However, these synthetic routes were too expensive to be commercially viable in competition with natural indigo. In 1890, Karl Heumann discovered two new synthesis processes. Having recognised Heumann’s breakthrough, Farbwerke ML&B and BASF both acquired the rights to his invention and to adapt these chemicals for their production processes. Around 1900, and after 100 patents, the German dye factories BASF and Farbwerke ML&B were able to produce Indigo synthetically in an economically affordable way. Three developments led to a rapid fall in the price of synthetic Indigo: the Pfleger process exploited by Farbwerke ML&B; the newly developed synthetic blue sulfur dyes of the German companies Cassella, Kalle and Bayer, which were strong competitors to synthetic Indigo, and the discovery of Indanthrene blue by René Bohn. But even today, after more than 125 years, synthetic Indigo is still popular. This chapter will focus on synthetic Indigo routes, their advantages, problems and limitations seen from a historical and economic perspective.