Cell-to-cell interactions are essential for proper development, homeostasis, and complex syncytia/organ formation and function. Intercellular communication are mediated by multiple mechanisms including soluble mediators, adhesion molecules and specific mechanisms of cell to cell communication such as Gap junctions (GJ), tunneling nanotubes (TNT), and exosomes. Only recently, has been discovered that TNTs and exosomes enable the exchange of large signaling molecules, RNA, viral products, antigens, and organelles opening new avenues of research and therapeutic approaches. The focus of this review is to summarize these recent findings in physiologic and pathologic conditions.