Advances in infant cardiac surgery have resulted in a dramatic decline in mortality rates; however, neurological morbidity remains an important concern. The effectiveness of a number of interventional strategies to prevent or minimize brain injury during open heart surgery are currently being investigated. This article provides an overview of two approaches: (1) interventions to enhance intraoperative cerebral oxygenation so as to prevent hypoxic-ischemic insults, and (2) the application of cerebral rescue therapies to attenuate the cascade of brain injury. Infant cardiac surgery provides a controlled environment in which to apply these neuroprotective approaches, so as to optimize the quality of life of these vulnerable children.