The NINDS trial demonstrated for the first time the effectiveness of intravenous thrombolysis in improving outcome after acute ischemic stroke. The absolute benefit of this intervention was 11-13% greater chance of being normal or near normal (MRS  1) at 3 months. However, if patients with severe stroke were considered (NIHSS  20), the absolute benefit dropped to 5-6%, indicating that IV thrombolysis may not be as effective for large vessel occlusion. This observation was further supported by TCD studies that clearly demonstrated that large artery occlusions had a recanalization rate of 13-18% with IV rt-PA. Intra-arterial thrombolysis achieves recanalization rates of 60-70%. Since tissue viability is clearly important, it is time to stop defining rigid time windows and if there is a large penumbra (20-50%) and the occlusion is in a large artery, there exists a logic and a growing evidence to consider either bridge therapy or direct intra-arterial therapy.