Regional citrate anticoagulation (RCA) is currently the recommended anticoagulation modality for continuous renal replacement therapy. Indeed, compared with systemic heparinization, RCA is associated with a lower risk of bleeding, a longer circuit lifespan and a decrease nursing workload. However, RCA requires a strict protocol to be followed, as it might be associated with potentially severe complications, such as citrate accumulation. Citrate accumulation is rare and usually associated with specific situations : severe circulatory shock, liver failure and mitochondrial dysfunction. According to centers' expertise, these situations might represent contra-indications to RCA. This review presents RCA, its mode of action, associated risks and proposes an algorithm for patients' selection.