Red cell concentrate is a life-saving but expensive and sometimes limited resource. Its use is associated with a wide range of rare but potentially severe complications. Adequate red cell transfusion is critical in terms of costs, resource utilization and safety. Transfusion thresholds have been widely debated and recent evidence suggest that a restrictive transfusion strategy may allow safely reducing the use of red cell concentrates and even improving clinical outcomes in some situations. The aim of this article is to review the physiologic adaptive responses to anemia and to discuss the clinical evidence about erythrocyte transfusion strategies in adult patients in order to provide evidence-based transfusion recommendations.