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Extracellular vesicles (EV), in particular exosomes, have been the object of intense research, due to their potential to mediate intercellular communication, modulating the phenotype of target cells. The natural properties and functions of EV are being exploited as biomarkers for disease diagnosis and prognosis, and as nano-bio-carriers for the development of new therapeutic strategies. EV have been particularly examined in the field of cancer, but are also increasingly investigated in other areas, like immune-related diseases and regenerative medicine.In this review, the therapeutic use of EV as drug delivery systems is described, balancing the advantages and drawbacks of different routes for their in vivo administration. Systemic and local delivery of EV are discussed, tackling the persisting difficulties in the assessment of their pharmacokinetics, pharmacodynamics and biodistribution in vivo. Finally, we discuss the future perspectives for incorporating EV into delivery systems and their use for an improved and controlled release of EV in vivo.