Acute occlusion of a peripheral artery is a catastrophic event. Whether resulting from in situ thrombosis of a native artery, a bypass graft, or embolization, acute limb ischemia threatens both the patient's limb and life. Traditionally, open surgical intervention has been the “gold standard” for treatment of these patients. However, the multiplicity and complexity of medical comorbidities account for high rates of perioperative morbidity and mortality. Thus, a minimally invasive alternative to open surgery is desirable, provided that the rate of limb salvage remains similar and other untoward events are infrequent. Catheter-directed thrombolytic therapy has been studied in this regard, offering the potential to restore arterial perfusion without the need for open surgery in many cases. In addition, thrombolysis can clear thrombus from small arteries that are inaccessible to a balloon catheter. Lastly, successful thrombolysis may unmask the lesion responsible for the occlusion and allow a directed, sometimes less invasive treatment. Thrombolysis has been criticized, however, on the basis of associated hemorrhagic complications, a slow rate of thrombus dissolution, and a higher risk of rethrombosis. This article explores the available data and, in this manner, provides an analysis of open surgery and thrombolytic therapy as initial interventions in patients with lower limb ischemia.