Absence of urokinase from the United States market for the past 4 years has resulted in increasing experience with other plasminogen activators in catheter-directed thrombolytic therapy. The differences in the pharmacologic properties and biologic behavior of these agents may translate into clinical outcomes that are distinct. Some of these manifestations can be predicted based on the existing large clinical trials in the acute myocardial infarction literature. However, because of the fundamental differences in techniques and thrombolytic regimens, extrapolation of the coronary data may not always predict the performance of these agents in peripheral catheter-directed fibrinolysis. In this article, the current status of the available lytic agents in the treatment of limb ischemia is reviewed.