Acute Abdomen: When Not to Operate? Acute abdomen is not a disease on its own but a description of a symptom complex, with very severe abdominal pain existing for less than 24 h. Via an interdisciplinary approach one has to clarify, as fast as possible, whether an operation is mandatory. This should be possible by ‘intelligent’ application of only a few but utmost important diagnostics. The aim of these procedures is to come quickly and effectively to the correct diagnosis. In most cases of acute abdomen there is an indication for immediate surgery. From a gastroenterological conservative view, acute pancreatitis is a disease which may present as acute abdomen but rarely needs a surgical approach. Of clinical importance, but a rare condition, is pseudoperitonitis diabetica. Non-ulcer dyspepsia, irritable bowel syndrome, uncomplicated peptic ulcera, acute gastroenteritis, viral hepatitis, inflammatory bowel diseases without complications, mesenterial lymphadenitis, or acute pyelonephritis may cause pain but very rarely imitate an acute abdomen. Acute porphyria, intestinal pseudo-obstruction and hemolytic crisis represent rare diseases in which a surgical approach is the wrong decision. Finally, there are numerous rarities such as gastrointestinal bleeding of various localizations under anticoagulation therapy which may cause symptoms of acute abdomen and may be managed by conservative or minimally invasive procedures. However, not only gastroenterological diseases but also pulmonary, cardiac, metabolic, renal, or gynecological (i.e., ectopic pregnancy, salpingitis, endometriosis, ovarial cysts) disorders may lead to an acute abdomen. In this review, considerations concerning differential diagnosis and an interdisciplinary approach are discussed. The important aim is to not postpone a mandatory operation as well as to avoid unnecessary laparotomies.