Platelet transfusions play an important role in the treatment of critically ill patients. Like any blood component, however, there are various aspects of platelet transfusion therapy that need be considered by the intensivist. These include the proper dose and type of platelet component to infuse, as well as the route and method of administration. Methods to reduce the volume of the transfused platelets, for example, must ensure that the infused platelets will be functional and viable, posttransfusion. Treatment and diagnosis of the HLA alloimmunized recipient can pose a serious challenge to the clinician and an obstacle to adequate platelet therapy. An ICU patient for whom an adequate posttransfusion platelet increment cannot be achieved is at great risk of suffering a fatal hemorrhage. The ICU physician should be aware of the techniques used in modern transfusion practice to avoid having to deal with this complication. Adverse reactions to platelet transfusion include not only serologic ones, but those related to febrile and allergic complications, as well as infectious complications. The latter group includes diseases caused by infection with cytomegalovirus, bacteria, and a cadre of viruses including HIV and hepatitis. The clinical approach to thrombocytopenia in the ICU will be covered in some detail in an effort to review many of the conditions associated with recipient thrombocytopenia, including ITP, TTP, dilutional thrombocytopenia, DIC, surgery, HELLP syndrome, and drug-induced thrombocytopenia. Unfortunately the treatment approaches traditionally used are not always derived from evidence-based studies. This review covers many of these topics in an attempt to help physicians become better able to manage thrombocytopenia in the ICU and thus provide the best transfusion therapy for their patients.