The human intestine is colonized by a complex microbial ecosystem, which could be considered as a separate organ within the human host, having a coding capacity which exceeds the liver by a factor 100. On the one hand, this extensive microbiome is closely involved in the first-pass metabolism and bioavailability of food and drug compounds. Understanding to which extent each individual ’ s gut microbiota affects the bioavailability and response to orally administered drugs is therefore a first important challenge towards novel drug development strategies. On the other hand, as our microbiota is directly or indirectly involved in the onset of a number of disease states, a new generation of therapeutics may be developed that affect the structure and functioning of the intestinal microbiota and interfere with their specific cross-talk with the human host. Ultimately, the intestinal microbiota may even be used as a biomarker for impending diseases inside or outside the gastrointestinal tract and for the evaluation of responses to specific therapeutic interventions. This review will therefore highlight the importance of the indigenous microbial community and its enormous metabolic potential, microbe-microbe interactions, mechanisms of host-bacterium cross-talk and will discuss the onset of obesity, a specific disease state in which the role of intestinal bacteria becomes more and more apparent. Understanding the importance of the intestinal ecosystem in these phenomena may open the door for new strategies which target the management of the intestinal microbiome into the desired direction and therefore to a completely new type of nutrition research and pharmaceutical design.