Simple SummaryExtracellular vesicles (EVs) are vehicles of cell communication that are able to carry several types of biomolecules derived from parent cells which, in a cancer context, can represent an oncogenic behavior, delivering them to recipient cells. Additionally, EVs present advantageous features, namely biocompatibility and high stability, which make them useful as delivery systems of new potential anticancer drugs. In fact, EVs can be used for the delivery of siRNAs, miRNAs, proteins, and nanoparticles in different diseases contexts. In this review, we highlight the potential application of EVs as drug delivery systems and their clinical applications.AbstractA deeper understanding of the communication mechanisms of tumor cells in a tumor microenvironment can improve the development of new therapeutic solutions, leading to a more personalized approach. Recently, the field of extracellular vesicles (EVs) has drawn attention due to their key role in intercellular communication. EVs are nano-sized lipid bilayer vesicles that are secreted by all types of cells and can function as intermediators of intercellular communication with the ability to transfer different cargo (proteins, nucleic acids, sugar…) types among cells. This role of EVs is essential in a cancer context as it can affect tumor promotion and progression and contribute to the pre-metastatic niche establishment. Therefore, scientists from basic, translational, and clinical research areas are currently researching EVs with great expectations due to their potential to be used as clinical biomarkers, which are useful for disease diagnosis, prognosis, patient follow-up, or even as vehicles for drug delivery due to their natural carrier nature. The application of EVs presents numerous advantages as drug delivery vehicles, namely their capacity to overcome natural barriers, their inherent cell-targeting properties, and their stability in the circulation. In this review, we highlight the distinctive features of EVs, their application as efficient drug delivery systems, and their clinical applications.