Extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communications in local and distant microenvironments under patho/physiological conditions. EVs contain bioactive materials such as proteins, RNA transcripts, microRNAs and even DNAs, and recent work on their protein profiles has revealed the existence of metalloproteinases including the cell surface-anchored sheddases ADAMs (a disintegrin and metalloproteinases) and soluble ADAMTSs (ADAMs with thrombospondin motifs) as well as cell surface-bound and soluble MMPs (matrix metalloproteinases) from various cell types and body fluids. EV-associated metalloproteinases can alter the make-up of EVs by ectodomain shedding, exert a shedding activity after being taken up by target cells, or directly contribute to degradation of extracellular matrix surrounding cells. In addition, metalloproteinase-loaded EV cargoes sometimes stimulate critical signaling pathways, actively participating in tumor progression. This review focuses on recent findings and knowledge about metalloproteinases in EV biology, and we discuss their potential involvement in human diseases, highlighting the context of tumor cells and their microenvironment. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman.