The ability of a cell to receive signals from other cells and then translate them into changes in cell behavior plays crucial roles in development and tissue homeostasis. However, the deregulation of these carefully orchestrated events underlie the onset or progression of several diseases in the adult organism (1, 2), highlighting the need to better understand the mechanisms through which cells communicate with each other. When considering various examples of cellcell communication, the well-established growth factor receptor signaling paradigm comes to mind (2). In this case, one cell secretes a soluble growth factor into the extracellular environment. The growth factor then binds to its corresponding receptor expressed on the surface of a second cell, resulting in its activation and the initiation of intracellular signaling events that control a myriad of cellular processes ranging from promoting cell growth and differentiation to cell death and migration. In PNAS, Kanada et al.(3) investigate what is emerging as a new and exciting mechanism used by cancer cells to communicate with their environment. It entails the ability of cells to generate and release two types of cargo-containing vesicular structures, collectively referred to as extracellular vesicles (EVs) that are generally believed to differ in their biogenesis and certain physical properties (4-6). One of these types of EVs is exosomes, which are generated as a result of trafficking multivesicular bodies containing endosomes from the cytosol to the cell surface. The multivesicular bodies then fuse with the plasma membrane, releasing the endosomes (now widely referred to as exosomes) into the extracellular space. Most studies that have analyzed exosomes indicate that they range in size from 30 to 80 nm in diameter. Microvesicles (MVs), which represent the other major class of EVs, are considerably larger than exosomes (200-1,500 nm in size) and are generated as an outcome of plasma membrane budding (Fig. 1A). Both exosomes and MVs are able to engage and transfer their cargo to other (recipient) cells, whereupon they significantly influence cellular processes (7-10). In their study, Kanada et al. isolated the different populations of EVs produced by HEK293FT cells and meticulously compared their physical properties, ability to be loaded with different types of cargo, and function. Their findings not only challenged some of the central dogmas in the field but also raised the interesting possibility that EVs might provide an effective delivery mechanism for gene therapy. Although the study of EVs is in many ways still in its infancy, it is attracting a good deal of attention for several reasons. The first, and perhaps most important of these, is because of the contents of EVs. Exosomes and MVs have each been shown to contain a variety of cargo not typically thought to be released by viable cells, including cell surface receptors, cytosolic and nuclear proteins, metabolic enzymes, RNA transcripts, micro-RNAs, and even DNA (4-6). Although the contents of EVs often contain distinguishing signatures that allow them to be traced back to their cell of origin, it is worth emphasizing that the contents of EVs are specific and not simply a random sampling of the proteins and nucleic acids that comprise the cell (7, 9). Indeed, how certain proteins and different types of nucleic acids are routinely incorporated into EVs by cells, whereas others are apparently excluded, is just one of the many intriguing questions surrounding this new area of cell-cell communication. In all likelihood, specific intracellular mechanisms are in place to ensure that the proper protein and nucleic acid cargo is incorporated into the different classes of EVs (6 …