Basilar artery occlusion is a devastating condition with a poor prognosis and is the most severe manifestation of acute ischemic stroke caused by large vessel occlusion. Randomized evidence of the safety and efficacy of intravenous thrombolysis in this type of stroke is scarce, especially outside the standard time window of 0–4.5 hours. Tenecteplase has a higher potency on plasmin compared to alteplase and a longer half-life of the third generation. Increasing randomized and observational evidence supports the superiority of tenecteplase over alteplase in patients with acute ischemic stroke, particularly in large-vessel occlusion. This superiority is manifested by an improvement in the 3-month functional outcome assessed by the modified Rankin Scale (mRS). The commentary focuses on the use of intravenous tenecteplase within 24 hours of symptom onset in basilar artery occlusion.