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Stroke occurs when a cerebral blood vessel is blocked or ruptured, and it is the major cause of death and adult disability worldwide. Various pharmacological agents have been developed for the treatment of stroke either through interrupting the molecular pathways leading to neuronal death or enhancing neuronal survival and regeneration. Except for rtPA, few of these agents have succeeded in clinical trials. Recently, with the understanding of the pathophysiological process of stroke, there is a resurrection of research on developing neuroprotective agents for stroke treatment, and novel molecular targets for neuroprotection and neurorestoration have been discovered to predict or offer clinical benefits. Here we review the latest major progress of pharmacological studies in stroke, especially in ischemic stroke; summarize emerging potential therapeutic mechanisms; and highlight recent clinical trials. The aim of this review is to provide a panorama of pharmacological interventions for stroke and bridge basic and translational research to guide the clinical management of stroke therapy.