Red blood cell transfusion (RBCT) threshold in patients with sepsis remains a matter of controversy. In this review, we report a summary of the benefits and risks of RBCT. We then focus on the latest studies addressing this controversy, including the randomized controlled trials dealing with the early goal-directed therapy, the randomized controlled trials comparing liberal versus restrictive transfusion strategies, and finally the cohort studies assessing the impact of RBCT. The conclusions of these studies no longer argue for a 10 g/dL (30% hematocrit) transfusion threshold during the early phase of septic shock. Similarly, following the initial stabilization, most septic patients can be managed with a restrictive transfusion strategy using a 7 g/dL hemoglobin threshold. A more liberal transfusion strategy should be adopted if patients are not stabilized or for patients at risk of bleeding, with myocardial ischemia, or oncohematologic patients with potential hemostasis disorders. Triggers of RBCT other than hemoglobin level, more related to macrocirculation or microcirculation failures, should be developed to decide RBCT in septic patients.