Plant secretomics is a newly emerging area of the plant proteomics field. It basically describes the global study of secreted proteins into the extracellular space of plant cell or tissue at any given time and under certain conditions through various secretory mechanisms. A combination of biochemical, proteomics and bioinformatics approaches has been developed to isolate, identify and profile secreted proteins using complementary in vitro suspension-cultured cells and in planta systems. Developed inventories of secreted proteins under normal, biotic and abiotic conditions revealed several different types of novel secreted proteins, including the leaderless secretory proteins (LSPs). On average, LSPs can account for more than 50% of the total identified secretome, supporting, as in other eukaryotes, the existence of novel secretory mechanisms independent of the classical endoplasmic reticulum-Golgi secretory pathway, and suggesting that this non-classical mechanism of protein expression is, for as yet unknown reasons, more massively used than in other eukaryotic systems. Plants LSPs, which seem to be potentially involved in the defense/stress responses, might have dual (extracellular and/or intracellular) roles as most of them have established intracellular functions, yet presently unknown extracellular functions. Evidence is emerging on the role of glycosylation in the apical sorting and trafficking of secretory proteins. These initial secretome studies in plants have considerably advanced our understanding on secretion of different types of proteins and their underlying mechanisms, and opened a door for comparative analyses of plant secretomes with those of other organisms. In this first review on plant secretomics, we summarize and discuss the secretome definition, the applied approaches for unlocking secrets of the secreted proteins in the extracellular fluid, the possible functional significance and secretory mechanisms of LSPs, as well as glycosylation of secreted proteins and challenges involved ahead. Further improvements in existing and developing strategies and techniques will continue to drive forward plant secretomics research to building comprehensive and confident data sets of secreted proteins. This will lead to an increased understanding on how cells couple the concerted action of secreted protein networks to their internal and external environments.