Over the last decade, an extensive amount of evidence has accumulated which implicates PMN in the etiology and pathophysiology of ischemic/thrombotic diseases. It has become apparent that PMN infiltration is not, as once thought, an innocent secondary phenomenon following ischemia. Rather, PMN are active participants in the pathophysiology of infarction, exacerbating the tissue damage. Since the development of means to achieve reperfusion after thrombosis, this phenomenon has become of critical importance. Many different approaches, targeted at prevention of PMN trapping in the capillaries of the ischemic, area, have been shown to effectively reduce the final infarct size, and will likely prove valuable adjuncts to reperfusion. However, perhaps the most significant aspect of the realization that PMN play a significant role in thrombotic disease may prove to be the potential for early intervention: Elevated PMN counts are predictive of ischemic events, and there is preliminary evidence that the elevated PMN count may be also associated with increased PMN activation, suggesting that research directed at the prophylactic use of anti-PMN agents might someday prove effective in reducing the incidence of MI and stroke.