The human epigenome may link environmental exposures and commensal microbiota changes to host pathology in respect to the developmental origins of inflammatory bowel diseases (ulcerative colitis [UC] and Crohn's disease [more appropriately Crohn disease, CD]). Genetic predisposition - prenatal, perinatal and pediatric environmental influences - microbiome aberration (dysbiosis) and immune dysregulation appear to be important elements in disease development, progression and maintenance. The prevalence of combined genetic and epigenetic susceptibility toward UC and CD is calculated herein to be as high as 2%, and approximately 1% for UC and CD in highly developed countries, respectively. This review emphasizes the significant challenges for epigenetic research in inflammatory bowel diseases. Overcoming these challenges, however, could reveal unique opportunities for disease prevention, treatment and possible cure.