In the era of personalised medicine new biomarkers are required to early diagnose Sjögren's syndrome (SS), to define different disease subsets and to direct patients' clinical management and therapeutic intervention. In the last few years, several efforts have evaluated saliva proteome to detect and monitor primary SS. Although clinically valuable, these studies presented some limitations that have partially prevented the use of salivary biomarkers in clinical practice. Nowadays, proteomic of extracellular vesicle (EV) represents an emerging and promising field in the discovery of -omic biomarkers for pSS. EV is a relatively new term that includes exosomes, microvesicles and apoptotic body. EVs are packed with proteins, growth factors, cytokines, bioactive lipids, but also nucleic acids and in particular: mRNA, microRNA, long non-coding RNA, tRNA and rRNA. Therefore, they may represent a useful source for diagnostic, prognostic and therapeutic biomarkers in several conditions. In this review we will specifically focus on EV proteomics as a tool for the identification of novel biomarkers for pSS. In the first part we focused on the state of the art of the studies on proteomics in SS existing in the literature. In the second part we provided a definition of EV with an update on biological sample collection and processing for EV proteomic studies. Finally, we summarised the state of the art of EV -omics in SS highlighting the potential advantages of this novel approach compared to the overall traditional concept of analysing the proteome of blood or saliva.