Neurosurgical procedures can be complicated by significant blood losses that have the potential to decrease tissue perfusion to critical brain tissue. Red blood cell transfusion is used in a variety of capacities both inside, and outside, of the operating room to prevent untoward neurologic damage. However, evidence-based guidelines concerning thresholds and indications for transfusion in neurosurgery remain limited. Consequently, transfusion practices in neurosurgical patients are highly variable and based on institutional experiences. Recently, a paradigm shift has occurred in neurocritical intensive care units, whereby restrictive transfusion is increasingly favored over liberal transfusion but the ideal strategy remains in clinical equipoise. The authors of this study perform a systematic review of the literature with the objective of capturing the changing landscape of blood transfusion indications in neurosurgical patients.