Stroke and its disability have deserved the notoriety of a severe and potentially lethal condition, whose treatment is still challenging. The widely craved result of saving as much as possible from the neural tissue and eventually reviving what is thought to be in the ischemic penumbra – if not already dead and gone – is the outcome every clinician is dreaming of. There are several reviews on the issue, which have discussed several options of achieving neuroprotection in acute ischemic stroke. Of course, reviews are not and do not pretend to be exhaustive; new drugs enter repeatedly in the scene. We would limit our comments on some of the pharmacological agents, that although seem to be worldwide available, are still looking for obtaining the citizenship in the therapeutic armamentarium of acute ischemic stroke.