PURPOSE OF REVIEW: Knowledge on and understanding of the pathophysiology of inflammatory bowel disease (IBD) is continuously growing. Important insights from the last years are summarized in this review. RECENT FINDINGS: Further genetic risk factors for IBD have been identified and confirmed. Novel studies analyzing the function of these susceptibility factors have improved our understanding of specific pathophysiological pathways. Both the innate and the adaptive immune systems appear to be deregulated. The current notion that only about 25% of genetic heritability is explained by the published findings is being challenged. Epigenetic changes triggered by environmental factors probably contribute to heritability. Such environmental factors have been shown not only to influence immunological function and the intestinal barrier, but they also affect the composition of the gut microbiome and its interaction with the mucosal immune system. The gut microbiome, innate defense mechanisms and barrier function regulate each other, contributing to a balance that determines physiological or pathological inflammation. SUMMARY: New therapies will emerge from the concept of a multidirectional interplay between environment and microbiome on one hand and defense mechanisms on the other.