Routine platelet transfusions for patients with acute leukemia were introduced in the early 1960s, and since then platelet use has increased steadily. Despite widespread use, good clinical evidence supporting prophylactic platelet transfusions is limited, and there are very few studies that have examined the dose for prophylactic platelet transfusions. Review of the platelet dose used in both early studies of routine platelet transfusions and more recent clinical trials of platelet transfusions shows wide variation in dosing, which is also reflected in clinical practice. As such, only limited recommendations for platelet dose have been forthcoming from consensus conferences or guidelines. The results from 3 recent clinical trials and a mathematical model examining the dose for prophylactic platelet transfusions suggest that lower dose transfusions may decrease the total number of platelets transfused; however, no definitive conclusions about the optimal platelet dose can be reached as these trials were not designed to evaluate bleeding outcomes or total platelet utilization. Future large clinical trials of platelet dose, which examine these critical outcomes, are required. Only with these results can the optimal platelet dose be determined.