Microparticles are circulating fragments derived from blebbing and shedding of cell membranes through several mechanisms that include activation, apoptosis and cell damage. In the past they were largely considered as unimportant cell “dust”, but more refined detection techniques have revealed large variations in their relative proportion and concentration in numerous disease states. Importantly, these conditions include the most prevalent causes of death and disability in our societies, namely cardiovascular, neoplastic, and inflammatory diseases. Microparticles carry procoagulant, proapoptotic and neoangiogenetic materials in the blood stream, and can also be viewed as a technique cells may adopt to rapidly modify their phenotype, independently from genetic signals. In this review, we focus on the role of these very small ( < 1 micron) particles, not only as mere markers of an underlying pathologic state, but also as primordial intercellular messengers and defense mechanism that every viable cell can exploit in distress conditions. In this view, we suggest that this old communication system could be the target of future high-tech interventions, with potential broad consequences.