Extracellular vesicles (EVs) are small vesicles released by donor cells that can be taken up by recipient cells, playing a crucial role in cell-to-cell communication. EVs can carry nucleic acids and proteins, which can significantly impact the phenotype of the recipient cell. For this phenotypic effect to occur, EVs must fuse with the target cell membrane, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest due to their deregulation in diseases like cancer and their potential as drug delivery vehicles. Understanding the molecular mechanisms of EV uptake is essential. This review summarizes current knowledge on EV uptake mechanisms, including clathrin-dependent endocytosis, caveolin-mediated uptake, macropinocytosis, phagocytosis, and lipid raft-mediated internalization. The uptake mechanism may depend on proteins and glycoproteins on both the vesicle and the target cell surface. Further research is needed to understand the precise rules governing EV entry into cells.Extracellular vesicles (EVs) are small vesicles released by donor cells that can be taken up by recipient cells, playing a crucial role in cell-to-cell communication. EVs can carry nucleic acids and proteins, which can significantly impact the phenotype of the recipient cell. For this phenotypic effect to occur, EVs must fuse with the target cell membrane, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest due to their deregulation in diseases like cancer and their potential as drug delivery vehicles. Understanding the molecular mechanisms of EV uptake is essential. This review summarizes current knowledge on EV uptake mechanisms, including clathrin-dependent endocytosis, caveolin-mediated uptake, macropinocytosis, phagocytosis, and lipid raft-mediated internalization. The uptake mechanism may depend on proteins and glycoproteins on both the vesicle and the target cell surface. Further research is needed to understand the precise rules governing EV entry into cells.