The aim of neuroprotection is to rescue ischemic tissue and improve functional outcome by intervention on ischemic cascade. A lot of experimental trials demonstrated that neuroprotection is effective in infarction volume reduction. Unfortunately most of the effective agents in preclinical studies failed in clinical trials. None of tested neuroprotective agents have shown to improve outcome in clinical trial phase III up to now. The main reasons that may have caused the failure of past clinical trials are: extended therapeutic window, heterogeneous population of stroke patients, low dose administration, inadequate endpoints, discrepancies on outcome assessments in experimental and clinical trials, irregular study design and inadequate statistical evaluation. Future of neuroprotection is seen in concentration on the subgroup with existing penumbra, the combination of neuroprotection and thrombolysis and in prophylactic neuroprotection. The unification of the design in experimental and clinical trials is the main prerequisite for potential success in the clinical testing.