Significant advances have been achieved in the understanding of the pathogenesis of Crohn's disease (CD). A number of susceptibility genes have been detected by large genome wide screening-approaches. We do not completely understand the function of most of these genetic variants, however, there is good evidence that most of them are associated with the recognition and detection of luminal bacteria as well as defence against this microbiota. The important role of intestinal bacteria for the onset of CD is now clear. The intestinal bacteria and other "environmental" factors certainly contribute to CD pathogenesis: the respective genetic variations now termed as "susceptibility factors" exist since ten thousands of years. However, the incidence of CD is largely dependent on factors such as childhood hygiene or socioeconomic status; factors that are determined by living conditions and environment. New therapeutic concepts emerge from these insights. The most important progress in recent years certainly is the introduction of biologics in the therapy of CD. TNF blockers have been shown to be very effective for the control of complicated disease courses. However, more time will be needed until the concepts on pathogenesis evolve into new therapeutics that are introduced into clinical routine and guidelines. The hygiene hypothesis has led to the administration of helminths to CD patients to modulate the intestinal immune system. Another new approach is to improve the mucosal barrier function, which has been shown to be impaired in CD patients.