Bypass graft failure is an unsolved problem in the contemporary treatment of peripheral arterial occlusion. Thrombolysis of a failed bypass graft is performed with instillation of plasminogen activators directly into the substance of the thrombus. Thrombolytic techniques can restore the bypass graft to its pre-occlusive state, clearing the inflow and outflow tracts of propagated thrombus and unmasking the causative lesion responsible for graft occlusion. Open surgery, or an endovascular modality, can then be employed to directly address these lesions. Recent randomized trials have demonstrated the safety and efficacy of a thrombolytic treatment strategy when the graft occlusion is acute, that is, when the patient presents within 2 weeks of the event. The appropriate management of the patient with an acutely occluded bypass graft includes thrombolysis, endovascular modalities and open surgery, employed in conjunction, to improve patient outcome over that observed with an immediate operation alone.