Exosomes are a type of cell-derived extracellular nanovesicle. They relay information between cells. Some known exosome functions include immune modulation, promotion of angiogenesis, and tumor metastasis. To date, clinical use of exosomes has focused predominantly on evaluating their efficacy as cancer vaccines or diagnostically as biomarker containers. However, few investigations have explored their potential to serve as a platform for the development of semi-synthetic nanovesicles. Given their nanoscale size, potential to express targeting ligands in native conformations and deformable structure, exosomes offer a logical biological vesicle platform for adapting and producing semi-synthetic vesicles with excellent potential for nanomedicine applications. However, there are obstacles associated with realizing this potential that must be addressed. Thus, a systematic approach to isolating, modifying, and testing exosomes is presented to facilitate the introduction of exosome-based translational nanomedicine.