A variety of in vivo, in silico, in vitro, and ex vivo model systems are available to researchers for studying the human intestinal microbiome, its functionalities and complex interactions with the host. Different models serve different purposes, all of them having their relevance as well as limitations and interdependencies. This article by Alexander Maue and Randi Lundberg from Taconic provides an overview of the most popular model system concepts, how they are being employed in gut microbiome research, and how they are complementary to each other.