In Germany, as in most other industrialized countries, ischemic stroke is the leading cause of disability and the third leading cause of death. As the incidence of ischemic stroke increases with age it is expected that this problem will become even more urgent in an aging society. Despite significant research efforts on the clinical as well as on the experimental level, treatment of ischemic stroke is still based on general intensive care measures and on reperfusion therapy with recombinant tissue plasminogen activator (rtPA); however, rtPA is not suitable for a wide range of patients and is restricted to a therapeutic window of 4.5 h due to an increasing risk of bleeding. Accordingly, novel therapeutic options for ischemic stroke are urgently need. The current review discusses novel experimental therapeutic principles for ischemic stroke which may have clinical potential. The main topics are neuroprotection and strategies addressing the immune system.