Following the publication of recent retrospective and highly debated studies, transfusionists are increasingly asking for improved tools to assess the quality of transfusion-relevant products. At its dawn, proteomics emerged as a potential candidate for in-depth investigations of blood components and plasma derivatives. As its maturity is now at hand, the proteomic expertise seems to be ready to be massively transferred to the clinical setting, where it could be potentially used as a valid tool to test, from bench to bedside, the quality of collected blood components prior to or during storage. Proteomic strategies have been demonstrated to be also suited to verify the effects of the production and pathogen-reduction processes of plasma derivatives and blood components on the protein fractions, or to discover particular biomarkers readily adoptable for targeted evaluation of blood-component integrity or functionality. Although the technical background is in continuous and rapid expansion, the spread of proteomics in clinical routine practice has been hitherto hampered by high costs for dedicated facilities and specialized personnel.