A summary of putative mechanisms underlying the potential benefits and risks of platelet transfusions. Product and donation characteristics that may modify the efficacy and safety of platelet transfusions include ABO matching between donor and recipient, processing methods (eg, pathogen reduction technology, and storage media), and storage duration. Platelet and leukocyte activation leads to accumulation of proinflammatory cytokines (IL-1, -6, and -8 and transforming growth factor-β), soluble CD40 ligand, and formation of microvesicles. Platelet microvesicles become more numerous and injurious during storage and may trigger a recipient reaction, mediated by their molecular cargo, resulting in further inflammatory cytokine release. Platelet microparticles may downregulate macrophages and impair the reactivity of dendritic cells.