Since the pro-inflammatory cytokine IL-33 and its receptor (ST2) are closely involved in regulating both innate and adaptive immune responses, it is conceivable that they may play an important role in organ transplantation. IL-33 is broadly expressed by multiple cell types such as fibroblasts, epithelial cells, and endothelial cells. As a strong inducer of type 2 helper T (Th2) cellular immune responses, IL-33 can significantly prolong allograft survival in organ transplantation partially via altering gene expression profiles and increasing frequency of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Nevertheless, the IL-33 signaling pathway and its underlying mechanisms remain largely undefined in transplant biology. This present mini-review summarizes recent advances in the studies concerning the IL-33/ST2 signaling pathway and the analysis of its biological function in the field transplantation. The literature points to a deleterious role of activation of the IL-33/ST2 signaling pathway, giving rise to ischemia/reperfusion, acute kidney injury and failure, acute heart rejection, as well as liver fibrosis. Under pro-inflammatory conditions, IL-33 expression is upregulated. Alteration of IL-33 levels has been suggested as a biomarker for predicting organ injury and ongoing allogeneic transplant outcome. These studies have deepened our understanding of immunobiological role of IL-33 and its receptor in organ transplantation. Modulation of the IL-33/ST2 signaling pathway might be utilized as a therapeutic target in the clinic.