The supernatant potassium concentration [K+] of red blood cell (RBC) units is frequently much higher than normal human plasma potassium levels, especially in units nearing the end of their storage life. Clinical hyperkalemia resulting from RBC transfusions has been recognized as a transfusion complication for decades, and there have been reported cardiac arrests attributed to transfusion-associated hyperkalemia. This review summarizes the evidence surrounding RBC [K+] levels, effects of irradiation and washing on [K+], the evidence for clinical hyperkalemia and cardiac arrests resulting from transfusion, predictors of post-transfusion hyperkalemia, and their preventative strategies. Key points include: (a) the [K+] (in mmol/L) increases linearly and is approximately equal to the number of days of RBC unit storage; (b) irradiation causes a rapid increase in [K+]; (c) there is potentially sufficient potassium in the supernatant of current RBC preparations to lead to hyperkalemia with large transfusion volumes; (d) any rise in patient potassium after transfusion is usually transient due to the redistribution of the potassium load; (e) transfusion-associated hyperkalemic cardiac arrests probably do occur, although it is difficult to prove this fact conclusively; and (f) promising strategies to combat transfusion-associated hyperkalemia include RBC washing, the use of in-line potassium filters, and the use of traditional treatments for hyperkalemia such as the use of insulin.