To review role of environmental factors in the pathogenesis of Crohn's disease.We systematically reviewed trials and systematic reviews using PubMed and Web of science databases. Here, we review the current information on the causative factors and mechanisms of CD, including smoking, exercise, diet, animal protein, breastfeeding, history of childhood infection and vaccination, oral contraceptives, and antibiotics of CD. We also highlight important knowledge gaps that need to be filled in order to advance the field of CD research.Epidemiological studies have indicated the significance of environmental factors in the disease behavior and outcome of Crohn's disease (CD). There are a few recognized environmental factors, such as cigarette smoking, exercise, dietary habits, and breastfeeding, which are associated with the pathogenesis of CD. These factors are hypothesized to change the epithelial barrier function, which disturbs both the innate and adaptive immune systems and the intestinal flora. However, the effect of several risk factors, such as appendectomy and pharmaceutical use, differs across several studies, indicating the need for more rigorous research. Furthermore, few studies have examined effective interventions based on environmental factors that can improve disease outcomes. Recent studies have indicated that the pathogenesis of CD is related to environmental and genetic factors.We review the current information on the causative factors and mechanisms of CD, including smoking, exercise, diet, animal protein, breastfeeding, history of childhood infection and vaccination, oral contraceptives, and antibiotics of CD. However, further studies are needed to understand knowledge gaps in the field of CD.