Abstract: Acute ischemic stroke remarkably intensifies disability and morbidity, leading to heavy global burdens. It is caused by cerebral artery occlusion-mediated ischemic injury, accompanied by activation of neurons, astrocytes and oligodendrocytes. Its pathophysiological mechanisms mainly involve cellular energy failure, calcium overload, excitotoxicity, excessive generation of oxygen free radicals, inflammation and apoptosis. This review is focused on the progresses of novel research on the current status of clinical practice and potential mechanisms, including calcium overload, oxidative stress, apoptosis, autophagy and inflammatory immune-related signaling pathways, with a discussion of such therapeutic drugs as anti-excitotoxic, antioxidating, anti-nitro damage and anti-inflammatory agents, aiming to provide new approaches and evidence for the development and clinical application of new drugs.