Hemodialysis patients may die suddenly and unexpectedly from a number of causes. These may be divided into those deaths due directly to and occurring during hemodialysis, those deaths occurring while the patient is not undergoing dialysis, and those deaths that may occur at any time. The first group includes brain herniation, air embolism, acute hemorrhage as a result of machine malfunction or fistula rupture, electrocution, cardiac arrhythmia caused by hypokalemia, complications of subclavian intravenous catheter insertion, third-degree heart block as a result of triglyceride emulsion, and disseminated intravascular coagulation (DIC) or hyperkalemia caused by overheated dialysate. The second group includes deaths due to pericardial tamponade because of effusion and suicidal causes of death (exsanguination, electrolyte imbalance as a result of excessive intake of salt, fluid, or potassium) as well as more conventional methods of suicide. The last category includes people dying of arteriosclerotic cardiovascular disease, hypertensive cardiovascular disease, and internal hemorrhage. Investigation of these deaths, including pertinent historical, laboratory, and autopsy data and investigation of dialysis equipment, is discussed.