The gastrointestinal (GI) tract is one of the most studied compartments of the human body as it hosts the largest microbial community including trillions of germs. The relationship between the human and its associated flora is complex, as the microbiome plays an important role in nutrition, metabolism and immune function. With a dynamic composition, influenced by many intrinsic and extrinsic factors, there is an equilibrium maintained in the composition of GI microbiota, translated as “eubiosis”. Any disruption of the microbiota leads to the development of different local and systemic diseases. This article reviews the human GI microbiome’s composition and function in healthy individuals as well as its involvement in the pathogenesis of different digestive disorders. It also highlights the possibility to consider flora manipulation a therapeutic option when treating GI diseases.