Extracellular vesicles (EVs) are microparticles produced by all cell types in physiological and pathological conditions. Currently, two main types of EVs have been described, microvesicles (MVs) and exosomes, whose differences reside in the dimension as well as in the mechanisms underlying their generation. MVs are particles of 150–500 nm budding from the plasma membrane, whereas exosomes are nanovesicles of 20–100 nm formed intracellularly. Actually, the molecular mechanisms participating in EV biogenesis are known only in part. As far as their functions are concerned, two main hypotheses have been proposed: (i) EVs may act as a system for cell-to-cell communication by shuttling active biomolecules among cells, (ii) they could serve as vehicles for discharging damaged molecules (lipids and proteins) out of the cell, lightening the ubiquitin-proteasomal system as well as lysosomes in case of overload. In recent years, the interest for EVs increased exponentially starting from the observation that in many different diseases their number is significantly increased in the body fluids of patients (1–5). For this reason, EVs are currently under intense investigation for a possible employment in the clinical practice as prognostic biomarkers. Recently, our group reported MVs, derived from myeloid cells (monocytes, macrophages, and microglia), to be significantly upregulated in the cerebrospinal fluid (CSF) of patients with neuroinflammatory disorders, in particular of those suffering from the most severe forms of multiple sclerosis (6). The stimuli responsible for the production of such MVs from myeloid cells are not known, although the role of extracellular ATP (exATP) and its receptor P2X7 has been widely proven, albeit only in vitro; whether exATP recapitulates this effect also in vivo needs to be defined.