Multidetector CT (MDCT) is an imaging technique that provides otherwise unobtainable information in the diagnostic work-up of patients presenting with acute abdominal pain. A correct working diagnosis depends essentially on understanding the individual patient's clinical data and laboratory findings. In haemodynamically stable patients with acute severe and generalized abdominal pain, MDCT is now the preferred imaging test and gives invaluable diagnostic information, also in unstable patients after stabilization. In this descriptive review, we focus our attention on acute, severe and generalized or undifferentiated non-traumatic abdominal pain. The main differential diagnoses are acute pancreatitis, gastrointestinal perforation, ruptured abdominal aneurysm and acute mesenteric ischaemia. We will provide radiologist readers with a technical guide to optimize MDCT imaging protocols and list the major CT signs essential to reach a correct diagnosis and guide the best treatment.