In most patients coming to the general practitioner or specialist with a history of bloody diarrhoea, bacteria or drugs are the most likely causative agents and it will be possible to make a diagnosis fairly easily. Because of differences in treatment, ulcerative colitis (UC) and Crohn's disease (CD) must however seriously be considered especially in younger patients, with severe symptoms and whenever the history is prolonged. A variety of colitides may indeed be clinically confused with UC and CD. Pathological mimics that should not be missed include infectious diseases such as Campylobacter colitis, yersiniosis, amoebiasis and others; drug-induced diseases (due to nonsteroidal antiinflammatory drugs...); diverticular disease-associated colitis; intestinal endometriosis; intestinal vasculitis and Behçet's disease and iatrogenic conditions such as graft-versus-host-disease and radiation colitis. In most situations a precise diagnosis of these conditions should be possible when all data are available. The term "indeterminate colitis" is used, when a diagnosis of chronic idiopathic inflammatory bowel disease (IBD) is suggested, but the differential diagnosis between UC and CD can not be solved. This occurs in approximately 5% of all patients with IBD. Diagnostic problems can occur in acute fulminant colitis, acute prolonged colitis, chronic relapsing disease and pouchitis. Indeterminate colitis is essentially a temporary diagnosis. Surgical and medical treatment of these patients can be difficult. When surgical treatment is indicated, the type of surgery must be seriously considered. The clinical course of patients with indeterminate colitis is usually more severe when compared with classical UC and these patients require often more severe medical treatment. Diagnostic problems can also arise in longstanding IBD, either UC and CD. Relapse of symptoms can be due to intercurrent infection (CMV is one of the candidates). Medical treatment can influence the microscopic features and induce a discontinuous inflammation in UC, reminiscent of CD. In cases of doubt, the original biopsies should be reviewed to ascertain the diagnosis, and orient treatment.