Background: Cerebral protection is a key determinant of perioperative outcomes in aortic arch surgery. Despite significant advances, optimal strategies regarding temperature, perfusion modality, and cannulation site remain controversial, with heterogeneous evidence and lack of standardized protocols.

Methods: This narrative review summarizes experimental and clinical evidence from the last 15 years, focusing on the main determinants of cerebral protection: cerebral blood flow (CBF), autoregulation, perfusion pressure, temperature management, cannulation strategies, and antegrade (ACP) versus retrograde cerebral perfusion (RCP).

Results: Available evidence consistently shows that any form of cerebral perfusion is superior to no perfusion during circulatory arrest (CA). Selective antegrade cerebral perfusion (SACP) has progressively emerged as the most widely adopted strategy worldwide, supported by its more physiological flow pattern and encouraging clinical outcomes. Axillary artery cannulation is currently the preferred approach and is associated with a lower stroke risk compared to femoral access, although femoral cannulation remains a valid alternative in unstable patients requiring rapid cardiopulmonary bypass (CPB) initiation. Comparative studies between ACP and RCP demonstrate no clear superiority in terms of mortality or permanent neurological dysfunction (PND), particularly for short CA times. However, SACP may reduce temporary neurological deficits (TNDs). A global shift towards moderate-to-mild hypothermia combined with cerebral perfusion has been observed, with favorable outcomes. Nonetheless, substantial variability persists in perfusion parameters, including flow, pressure, and the choice between unilateral and bilateral cerebral perfusion.

Conclusions: Contemporary practice is moving toward strategies that better replicate physiological cerebral perfusion, favoring antegrade flow with moderate hypothermia. However, the lack of high-quality randomized evidence and persistent heterogeneity limit definitive recommendations, highlighting the need for standardized protocols and individualized approaches.