Decorin, a small leucine-rich proteoglycan (SLRP) family member, is a stromal proteoglycan approximately 90 to 140 kDa in molecular weight. It comprises a protein core with 12 leucine-rich repeats and a single glycosaminoglycan (GAG) chain composed of either dermatan or chondroitin sulfate. Synthesized primarily by fibroblasts, stressed vascular endothelial cells, and smooth muscle cells, decorin is known to interact with several matrix structural components, such as type I and type II collagen, fibronectin, thrombospondin, the epidermal growth factor receptor (EGFR) and the superfamily of transforming growth factor-beta (TGF-β) ligands. Originally, decorin was thought to act exclusively as a structural component playing key roles in matrix assembly and fibrillogenesis. However, recent discoveries have expanded the role of decorin to include angiogenesis, cell signaling, proliferation, differentiation, survival, adhesion, migration, and inflammatory response. The most notable discovery reveals decorin to be a promising cancer therapeutic agent due to its involvement in tumor development and progression. Decorin has been shown to inhibit tumorigenesis and growth in specific cells, has been utilized to treat tumor xenografts in gene therapy models, and can enhance cell survival by affecting signal pathways and cardiac-related activity.