We describe the case of a 74-year-old man with cholangitis, complicated by Clostridium perfringens septicaemia and massive intravascular haemolysis. Clostridium perfringens septicaemia is a rare but well-known cause of massive intravascular haemolysis. Here we review 40 similar cases published since 1990. Most cases involve immunocompromised patients with underlying haematological disorder (22.5%), pancreatic or gastric cancer (12.5%) and/or diabetes (30.0%). Focus of infection is mostly hepatobiliary (45.0%), intestinal or gynaecological after invasive procedure. Eighty percent of reviewed cases did not survive; the median time between admission and death was only eight hours. If an attempt was made to remove the focus of infection (i.e. by drainage of liver abscess, cholecystectomy, hysterectomy or ERCP), this proved to be a strong prognostic indicator of survival. However, in many of the cases the patient had already gone into shock or died before a diagnosis could be made. In severely ill patients with fever and haemolysis on the emergency department Clostridium perfringens septicaemia should always be considered, since early antibiotic treatment and if possible removal of the focus of infection can rescue patients from an otherwise fatal outcome.