Brain natriuretic peptide (BNP) is a marker of diagnosis and prognosis in patients with chronic heart failure. Stored in ventricular myocytes, it is released during ventricular stretch and increased transmural pressure. However, BNP behaves unusually after cardiac transplantation, with a failure to return to normal levels. This raises a question over whether other processes are involved in both its production and secretion. Several studies suggest BNP levels are associated with allograft rejection and coronary graft vasculopathy. Both of these processes have a single denominator in common, the activated immune system. This overview considers further evidence suggesting that BNP interacts with the immune system after cardiac transplantation.