In 1932, Burrill Bernard Crohn, Leon Ginzburg, and Gordon Oppenheimer published the paper "Regional ileitis: a pathological and clinical entity" first describing terminal ileitis that took further its name from B. Crohn. Crohn's disease (CD) is a recurring systemic inflammatory disease affecting the gastrointestinal tract (GIT) with extraintestinal manifestations and systemic immune disorders. Its etiology is unknown; the pathogenesis is associated with congenital impairments in the intestinal barrier and immune response to diversified symbiotic bacteria. The classification and the specific features of the natural history of CD are presented; the possibilities of new methods for its diagnosis and treatment are shown. Its new treatment goals are formulated; these are to achieve complete recovery of the involved bowel wall; to use confocal endoscopy, ultrasonography, magnetic resonance imaging, computed tomography, positron emission tomography, and the biomarkers C-reactive protein, fecal calprotectin, and lactoferritin. Algorithms for CD diagnosis and treatment using anticytokine agents and mesenchymal stromal stem cells are given.