The concept of preventive neuroprotection is based on experimental concept of brain ischemic tolerance in which a cerebral resistance against ischemia consequences is induced prior to its occurrence. Pharmacological agents mimicking the biological mechanisms observed in brain ischemic tolerance might increase the resistance of patients with high stroke risk to the deleterious effects of brain ischemia. Activation of cytoprotective proteins or regulation of deleterious molecular pathways could constitute the main pharmacological targets to induce preventive neuroprotection. Several pharmacological agents such as statins or fibrates have been demonstrated experimentally to induce a preventive neuroprotection related to their pleïotropic anti-inflammatory and antioxidant properties. In future, the prevention treatment of stroke occurrence may be completed by preventive neuroprotective treatment. Moreover, some drugs could have potentially both preventive and neuroprotective properties, which are likely linked.