Abstract: Extracellular vesicles (EVs) are cell-derived, lipid membrane-enclosed vesicles carrying a broad spectrum of biologically active molecules (including proteins, RNAs, and bioactive lipids) which play important roles in intercellular communication. EVs crucially control neuronal energy metabolism under physiological conditions, constrain oxidative stress and brain inflammatory responses, and promote neuronal survival and plasticity upon brain damage. Originating from the right cells, e.g., mesenchymal stromal cells (MSCs), EVs can exhibit striking neurological recovery-promoting activities in various brain disease models (Hermann et al., 2024). In rodent middle cerebral artery occlusion (MCAO) models, for example, intravenously administered MSC-derived EVs enhanced motor coordination recovery similar to parental MSCs by mechanisms involving long-term neuroprotection, neurogenesis, axonal sprouting, remyelination, and synaptic plasticity (Xin et al., 2013; Doeppner et al., 2015). In contrast to pharmacological compounds that target specific signaling pathways, EVs depending on their cellular origin exhibit multiple signaling abilities, enabling them to regulate several disease processes simultaneously in a clinically relevant way (Hermann et al., 2024). In the long term, EVs are expected to surpass and replace many current pharmaceuticals, as their multimodal mechanism of action can synergistically and contextually modify disease outcomes more effectively. The successful clinical translation will decisively depend on the selection of the right targets.