The selection of an appropriate therapeutic regimen, especially in patients with preexisting cardiac dysfunction prior to surgery, is a crucial element for successful separation from cardiopulmonary bypass (CPB). At the present time there are no definitive studies to determine which treatment modality, or combination of treatments, is optimal in this patient population. A brief review of the literature is presented to answer the following questions: (1) Should inotropic support be administered in anticipation of failure to wean from CPB? and (2) Which inotrope or combination of drugs is best? There is no evidence at present that the prophylactic administration of inotropes to assist separation from CPB may result in damaging effects to the myocardium in humans. Inasmuch as tachycardia is avoided and coronary perfusion pressure is maintained within the normal range, prophylactic inotropes may be of benefit to patients with preexisting myocardial dysfunction during weaning from CPB by allowing a smoother separation and a shorter time on CPB. While no specific drug has been proven superior, the use of phosphodiesterase inhibitors as part of the regimen to provide inotropic support in these patients may exert a beneficial effect on myocardial ischemia and reperfusion injury. Prophylactic support of the circulation during separation from CPB, especially with phosphodiesterase inhibitors, may be indicated in this specific patient population as part of the strategy to ensure maximal preservation of myocardial function.