Thrombolysis with intravenous alteplase is the primary therapy for acute ischemic stroke, and is approved in most countries. Early administration improves functional outcome though benefit and risk depend on the time elapsed between stroke onset and initiation of treatment. Randomized controlled trials demonstrated benefit from intravenous thrombolysis when initiated up to 4.5 hours after symptom onset, and pooled analysis of all trials indicates that the sooner that alteplase is given, the greater is the benefit. Treatment carries a risk of bleeding, with symptomatic intracranial hemorrhage (SICH) of around 3%. Initiating treatment after 4.5 hours increases mortality and reverses the risk-benefit balance. Baseline stroke severity, age, diabetes and concomitant stroke are associated with poorer outcome from acute stroke; but secondary analyses and controlled registry data suggest that intravenous alteplase remains effective in most subgroups. Intra-arterial thrombolysis has a less extensive evidence base and is mostly unapproved for acute stroke. Access to thrombolysis remains patchy and involves unacceptable delays: greater awareness of the benefits and time dependency are crucial.