Open-heart surgery is the leading cause of neuronal injury in the perioperative state, with some patients complicating with cerebrovascular accidents and delirium. Neurological fallout places an immense burden on the psychological well-being of the person affected, their family, and the healthcare system. Several randomised control trials (RCTs) have attempted to identify therapeutic and interventional strategies that reduce the morbidity and mortality rate in patients that experience perioperative neurological complications. However, there is still no consensus on the best strategy that yields improved patient outcomes, such that standardised neuroprotection protocols do not exist in a significant number of anaesthesia departments. This review aims to discuss contemporary evidence for preventing and managing risk factors for neuronal injury, mechanisms of injury, and neuroprotection interventions that lead to improved patient outcomes. Furthermore, a summary of existing RCTs and large observational studies are examined to determine which strategies are supported by science and which lack definitive evidence. We have established that the overall evidence for pharmacological neuroprotection is weak. Most neuroprotective strategies are based on animal studies, which cannot be fully extrapolated to the human population, and there is still no consensus on the optimal neuroprotective strategies for patients undergoing cardiac surgery. Large multicenter studies using universal standardised neurological fallout definitions are still required to evaluate the beneficial effects of the existing neuroprotective techniques.