Red blood cell (RBC) transfusion is a very common therapeutic intervention. However, because of multiple recent studies improving our understanding of appropriate transfusion scenarios, the total number of RBC units transfused per year is actually decreasing in the developed world and there are no longer major shortages of RBC products for general use. Nonetheless, there are an increasing number of “special” uses, which can put strains on the blood supply for particular types of products; these may produce shortages of specific types of RBCs or require collections targeting certain types of donors. This review will focus on several broad topics, including providing some examples of “special” settings that require, or could require, special types of RBC products.