Intercellular communications play a vital role during tissue patterning, tissue repair, and immune reactions, in homeostasis as well as in disease. Exosomes are cell-derived secreted vesicles, extensively studied for their role in intercellular communication. Exosomes have the intrinsic ability to package multiple classes of proteins and nucleic acids within their lumens and on their membranes. Here, we explore the hypothesis that exosomal targeting may represent a cellular strategy that has evolved to deliver specific combinations of signals to specific target cells and influence normal or pathological processes. This review aims to evaluate the available evidence for this hypothesis and to identify open questions whose answers will illuminate our understanding and applications of exosome biology.