Living organisms must adapt and communicate effectively in their environment to survive. Cells communicate through various mechanisms, including releasing growth factors, chemokines, small bioactive molecules, and cell–cell contact. In recent years, a new and sophisticated cell communication mechanism based on extracellular vesicles (EVs) has been described in all three domains of life: archaea, bacteria, and eukaryotes. EVs are small, bilayer proteolipid vesicles released by cells into the extracellular space. This review aims to analyze and compare the current literature on bacterial, archaeal, and eukaryotic EVs and their possible clinical applications. This framework will address three key points: (a) The role of EVs in bacteria, eukaryotes, and archaea. (b) What is the impact of EVs in archaea on disease? (c) How archaea use EVs to communicate with other domains (bacteria/eukaryotes).