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Ulcerative colitis is a life-long, chronic, relapsing and remitting inflammatory disease of the large intestine with an unpredictable course characterized by debilitating gastrointestinal symptoms accompanied by healthcare and emotional burdens that reduce the quality of life and the ability to work, attend school, and be productive. Ulcerative colitis affects millions of people worldwide and is now considered a global disease. Although some form of primary immune abnormality is thought to underlie this illness, extensive laboratory research conducted since the mid-20th century has largely failed to definitively establish a primary antecedent immune abnormality in individuals with ulcerative colitis or their family members. An alternative approach employing a systems pathogenesis analysis has implicated a causal role for colonocyte-generated hydrogen peroxide in the pathogenesis of this illness. Significantly elevated levels of hydrogen peroxide in non-inflamed colonic mucosa have been demonstrated in individuals with ulcerative colitis, implying a build-up prior to the onset of inflammation and supporting a causal role for colonocyte hydrogen peroxide in the development of this disease. Hydrogen peroxide's unique properties of cell membrane permeability, long life, potent oxidizing potential, and the ability to attract white blood cells combine to promote oxidative disintegration of colonic epithelial tight junctional proteins while attracting white blood cells into the colonic epithelium, both of which lead to colonic inflammation and eventual ulcerative colitis.