Recent advances in extracellular vesicle (EV) research have given rise to a new paradigm in cellular communication. EVs are small membrane vesicles released by cells that can be visualized by cryo-electron microscopy in a close to native state. The cover image shows vesicles released from skin cells called melanocytes and reveals their elegant but simple structure (for details see van Niel et al. (2015) Cell Rep. 13, 43-51). In this issue of Essays in Biochemistry, the role of EVs (exosomes and microvesicles) in extracellular communication has been approached from multiple perspectives: intracellular sorting and vesicle biogenesis, complex physiological systems including cardiovascular biology, metabolism and development, as well as pathophysiologic deviations including cancer and infection. Model organisms, key research tools in cell developmental biology research, have been highlighted as well. EVs, because of their role in cell-to-cell communication and their broad distribution across phyla and even kingdoms, represent a new frontier in biological and medical science. Image credit: Guillaume van Niel and Daniel Levy (Institut Curie).