This article reviews evidence for the involvement of cell-derived microparticles (MPs) in transfusion-related adverse events. The controversy concerning possible added risk of older versus fresher stored blood is also reviewed and is consistent with the hypothesis that MPs are involved with adverse events. Although all types of circulating MPs are discussed, the emphasis is on red blood cell–derived MPs (RMPs). The evidence is particularly strong for involvement of RMPs in transfusion-related acute lung injury, but also for postoperative thrombosis. However, this evidence is largely circumstantial. Work in progress to directly test the hypothesis is also briefly reviewed.