Imidazo[1,2-a]pyridine is a well-known scaffold in many marketed drugs, such as Zolpidem, Minodronic acid, Miroprofen and DS-1 and it also serves as a broadly applied pharmacophore in drug discovery. The scaffold revoked a wave of interest when Groebke, Blackburn and Bienaymé reported independently a new three component reaction resulting in compounds with the imidazo[1,2-a]-heterocycles as a core structure. During the course of two decades the Groebke Blackburn Bienaymé (GBB-3CR) reaction has emerged as a very important multicomponent reaction (MCR), resulting in over a hundred patents and a great number of publications in various fields of interest. Now two compounds derived from GBB-3CR chemistry received FDA approval. To celebrate the first 20 years of GBB-chemistry, we present an overview of the chemistry of the GBB-3CR, including an analysis of each of the three starting material classes, solvents and catalysts. Additionally, a list of patents and their applications and a more in-depth summary of the biological targets that were addressed, including structural biology analysis, is given.