Acute stroke therapies are evolving gradually. The heterogeneity of stroke has made it difficult to achieve success in large randomized trials. There appears to be "no shoe that fits all" in stroke treatment other than early systemic thrombolysis using recombinant tissue-type plasminogen activator (rt-PA), which succeeds by achieving early recanalization, thereby limiting infarct extent. Many lessons have been learned that have refined our approach to developing new treatments. Emerging therapies for stroke can be classified into a few basic themes. In ischemic stroke, promising therapies are aimed at optimizing arterial recanalization through combined systemic drugs, ultrasound-enhanced treatment, or the use of interventional techniques, such as intraarterial tissue plasminogen activator, Merci® catheter, or a combined systemic/interventional approach. Neuroprotection treatment remains elusive, although strategies to initiate ultra-early (ambulance-based) neuroprotection appear justified. Collateral flow augmentation techniques appear promising in improvement of cerebral blood flow via this backdoor approach. The extension of treatment windows beyond the first 3 hours is reliant on neurovascular imaging techniques such as CT perfusion and multimodal MRI to detect significant penumbra.