Crohn's disease and ulcerative colitis are the two main forms of inflammatory bowel disease. Inflammatory bowel diseases have a life time prevalence of up to 1 % in western industrialized countries. It is generally proposed that genetic susceptibility, which is much more widespread in the population, needs (unknown) factors in lifestyle in order to lead to disease manifestation. Systematic genome-wide association studies opened a new level of understanding of the risk architecture of inflammatory bowel diseases. This has led to the concept that barrier problems on the level of the intestinal epithelial cells may be a main driver in disease etiopathogenesis. Many of the newly discovered disease genes are not only relevant for inflammatory bowel disease but also for other disorders. This has initiated a large research interest in co-morbidities, which appear to be overlooked on the clinical side, too. Novel therapies should address the primary disease mechanisms and therefore provide causal interventions. Endpoints should include the avoidance of co-morbidities, which may be a limiting factor for patients with chronically active disease.