The article provides a comprehensive overview of the genetics and pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. It highlights recent advances in understanding the maintenance of mucosal immunity and the complex interactions between host, microbial, and environmental factors. The review discusses the role of genetic predispositions, particularly through genome-wide association studies (GWAS), which have identified numerous genetic risk loci for IBD. These loci are associated with pathways crucial for intestinal homeostasis, such as barrier function, epithelial restitution, microbial defense, and immune regulation. The article also explores the impact of environmental factors, such as smoking, on disease development and the role of specific genes and pathways in IBD pathobiology. Additionally, it delves into the intricate interactions between the intestinal epithelium, innate and adaptive immune cells, and the gut microbiota, emphasizing the importance of maintaining a balanced immune response to prevent IBD. The review concludes by discussing future perspectives, including the need to better understand the dynamic nature of the gut microbiome and its role in IBD pathogenesis.The article provides a comprehensive overview of the genetics and pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. It highlights recent advances in understanding the maintenance of mucosal immunity and the complex interactions between host, microbial, and environmental factors. The review discusses the role of genetic predispositions, particularly through genome-wide association studies (GWAS), which have identified numerous genetic risk loci for IBD. These loci are associated with pathways crucial for intestinal homeostasis, such as barrier function, epithelial restitution, microbial defense, and immune regulation. The article also explores the impact of environmental factors, such as smoking, on disease development and the role of specific genes and pathways in IBD pathobiology. Additionally, it delves into the intricate interactions between the intestinal epithelium, innate and adaptive immune cells, and the gut microbiota, emphasizing the importance of maintaining a balanced immune response to prevent IBD. The review concludes by discussing future perspectives, including the need to better understand the dynamic nature of the gut microbiome and its role in IBD pathogenesis.