Although the precise link between the increased incidence of allograft rejection in female heart transplant recipients remains uncertain, various gender-specific characteristics may predispose women to earlier rejection episodes. Critical care practitioners must be cognizant of the underlying immunologic factors that indicate higher risk in these recipients. Until the ideal treatment for cardiac rejection is discovered, identifying pertinent immunologic factors, attending to subtle symptoms, obtaining serial endomyocardial biopsies and initiating prompt, additional aggressive immunosuppressive protocols remain paramount in rendering quality patient care. Research must continue to elicit more specific tissue-typing antigens and more selective immunosuppressive agents that will ultimately result in prolonged survival of all heart transplant recipients.