Exosomes, naturally occurring nanocarriers, offer unique advantages for drug delivery due to their ability to specialize in cell-to-cell communication and deliver therapeutic agents to target cells. This review focuses on the development and validation of exosome-based drug delivery systems, discussing various techniques for exosome isolation, characterization, drug loading, and applications in experimental disease models and clinical settings. Exosomes can be modified to express targeting moieties or supplemented with desired biological activity, making them suitable for a wide range of disorders, including cancer, infectious diseases, cardiovascular issues, and neurodegenerative disorders. They combine the benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations. The review also highlights the natural functions of exosomes, such as immune regulation and protective and regenerative effects, and explores methods for drug loading into exosomes, including ex vitro loading, parental cell loading, and genetically modified parental cells. Finally, it discusses the potential of exosomal drug formulations in clinical settings, emphasizing the need for further research to address technological, functional, and safety challenges.Exosomes, naturally occurring nanocarriers, offer unique advantages for drug delivery due to their ability to specialize in cell-to-cell communication and deliver therapeutic agents to target cells. This review focuses on the development and validation of exosome-based drug delivery systems, discussing various techniques for exosome isolation, characterization, drug loading, and applications in experimental disease models and clinical settings. Exosomes can be modified to express targeting moieties or supplemented with desired biological activity, making them suitable for a wide range of disorders, including cancer, infectious diseases, cardiovascular issues, and neurodegenerative disorders. They combine the benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations. The review also highlights the natural functions of exosomes, such as immune regulation and protective and regenerative effects, and explores methods for drug loading into exosomes, including ex vitro loading, parental cell loading, and genetically modified parental cells. Finally, it discusses the potential of exosomal drug formulations in clinical settings, emphasizing the need for further research to address technological, functional, and safety challenges.