Careful assessment of risks and benefits has to precede each decision on allogeneic red blood cell (RBC) transfusion. Currently, a number of key issues in transfusion medicine are highly controversial, most importantly the influence of different transfusion thresholds on clinical outcome. The aim of this article is to review current evidence on blood transfusions, to highlight 'hot topics' with respect to efficacy, outcome and risks, and to provide the reader with transfusion guidelines. In addition, a brief synopsis of transfusion alternatives will be given. Based on up-to-date information of current evidence, together with clinical knowledge and experience, the physician will be able to make transfusion decisions that bear the lowest risk for the patient.