Safe and effective anticoagulation is the key to successful blood purification. Compared with traditional systemic anticoagulation, regional citrate anticoagulation (RCA) has the advantages of prolonging the life of extracorporeal circulation and reducing bleeding complications. However, the complex protocol, the disorder of electrolyte and acid-base status and the accumulation risk in special populations have dissuaded many clinicians. This review starts with the clinical monitoring of RCA, then analyzes the causes and treatments of complications. The risk assessments in special populations were also introduced in order to the widely promotion of RCA in critically ill patients.