Four approved plasma preparations are available in most European countries: fresh frozen plasma, lyophilized plasma, solvent/detergent(SD)-treated plasma and methylene blue/light-treated plasma. Evidence of the clinical efficacy of plasma is mainly based on controlled or uncontrolled observational studies, case reports or expert opinion. As definitions of evidence grades used in previous guidelines and recommendations are sophisticated and difficult to apply to clinical routine, we established a simple system involving 2 recommendation strengths (1 and 2) and 3 evidence grades (A, B, C). Plasma is indicated for complex coagulopathy associated with manifest or imminent bleeding, particularly microvascular bleeding, in massive transfusion, disseminated intravascular coagulation and liver disease. With the exception of emergency situations when clotting assay results are not available on time, a clinically relevant coagulopathy must be verified before plasma is administered. The rapid infusion of at least 10 ml of plasma per kg of body weight is required to increase the respective clotting factor or inhibitor levels significantly. Therapeutic plasma exchange with 40 ml of plasma per kg of body weight is the treatment of first choice in acute thrombotic-thrombocytopenic purpura (TTP) or adult hemolytic uremic syndrome (HUS). Rare indications are congenital factor V or FXI deficiency, plasma exchange in neonates with severe hemolysis or hyperbilirubinemia, and filling of the oxygenator in extracorporeal membrane oxygenation in neonates. Prothrombin complex concentrates should be preferred to plasma for the rapid reversal of oral anticoagulation, since plasma is less efficient in this setting. Side effects resulting from the administration of plasma are rare but have to be considered.