Inflammatory bowel diseases (IBD), mainly ulcerative colitis and Crohn's disease, are chronic, heterogenic, lifelong illnesses with young age of onset and a great potential for disability. The natural history of these diseases is influenced by multiple factors of environmental and genetic origin. Multidisciplinary research has increased our knowledge of the mechanisms involved during the development and outcome of the diseases, including disease complications. Immunomodulatory treatment has demonstrated greatly improved efficacy in moderate to severe disease activity. The long-term effect on the natural course of disease and sustained reduced burden on society over many years require study. This article summarizes recent knowledge on factors influencing the natural history of IBD, including the impact of treatment. Increased understanding of disease mechanisms is needed as a basis for new treatment strategies in the future.