Exosomes, nano‐sized extracellular vesicles, are produced via the endosomal pathway and released in the extracellular space upon fusion of multivesicular bodies with the plasma membrane. Recent evidence shows that these extracellular vesicles play a key role in cell‐to‐cell communication. Exosomes transport bioactive proteins, mRNAs, and microRNA (miRNAs) in an active form to adjacent cells or to distant organs. In this review, we focus on the role of exosomes in peripheral nerve maintenance and repair, as well as peripheral nerve/organ crosstalk, and discuss the potential benefits of exploiting exosomes for treating PNS injuries. In addition, we will highlight the emerging role of exosomes as new important vehicles for physiological systemic crosstalk failures, which could lead to organ dysfunction during neuroinflammation or aging.