Stroke is a devastating medical condition, killing millions of people each year and causing serious injury to many more. Despite advances in treatment, there is still little that can be done to prevent stroke-related brain damage. The concept of neuroprotection is a source of considerable interest in the search for novel therapies that have the potential to preserve brain tissue and improve overall outcome. Key points of intervention have been identified in many of the processes that are the source of damage to the brain after stroke, and numerous treatment strategies designed to exploit them have been developed. In this review, potential targets of neuroprotection in stroke are discussed, as well as the various treatments that have been targeted against them. In addition, a summary of recent progress in clinical trials of neuroprotective agents in stroke is provided.