The publication of the positive results of the National Institutes of Neurological Disease and Stroke (NINDS)1 trial of alteplase (a recombinant tissue plasminogen activator) for patients with acute stroke in 1995 and its approval by the US Food and Drug Administration as well as by the American Academy of Neurology and American Heart Association2 3 increased the interest and attention of the medical community for acute stroke treatment. However, the implication of this NINDS Stroke Study and other thrombolytic trials in clinical practice remains extremely controversial and debated. Furthermore, the recent publication of the results from the European Cooperative Acute Stroke Study II (ECASS II)4will feed the controversy as ECASS II4 results are disappointing and do not confirm the positive results of the NINDS Stroke Study.1 Consequently, what is the more reasonable position concerning thrombolysis by alteplase, and what seems to work has not been established yet beyond reasonable doubt. Numerous trials devoted to neuroprotection against acute ischaemic stroke have been prematurely stopped because of safety concerns or poor risk:benefit ratios, but some new neuroprotective drugs seem promising and are being tested. The third area of research in progress is the use of antithrombotic drugs in the acute phase of stroke. In this paper, we review selected recent clinical trials focusing on recent advances in acute stroke therapy.