The first description of microparticles dates back to 1967, when Wolf reported platelet membrane fragments in human plasma and called them “platelet dust”. These vesicles were later called microparticles and the knowledge about their characterization and function has advanced since then. The generation of microparticles represents a mechanism of intercellular communication, playing various roles in both physiological and pathological conditions. Besides other multiple roles in pathology such as inflammation, atherogenesis and cancer spreading, platelet-derived microparticles are involved in thrombogenesis. Tissue factor and phosphatidylserine are both exposed on the outer membrane of platelet-derived microparticles, providing catalytic procoagulant surfaces. The evaluation of microparticles may represent a possible investigation and diagnostic tool. Their enumeration and characterization is challenging and flow cytometry remains the most widely used method for the analysis of microparticles. The aim of the authors is to review the most relevant information on the main properties, mechanisms of generation, and clinical relevance of platelet-derived microparticles, since their evaluation is increasingly considered as a diagnostic biomarker.