Proteoglycans are ubiquitous molecules composed of glycosamino-glycan chains attached covalently to core proteins. Proteoglycans perform a myriad of functions and participate in regulating tumor cell growth, survival, adhesion, metastasis and angiogenesis. These functions are largely mediated through inter-actions between their charged glycosaminoglycan chains and effector proteins such as growth factors, cytokines and chemokines. In addition, emerging data is revealing that the core proteins of proteoglycans can also form complexes with other proteins such as integrins and regulate their signaling. Because proteoglycans are at the crossroads of many signaling events, they are currently being extensively investigated for their potential as therapeutic targets for cancer. This review focuses on the expression, structure and function of proteoglycans in cancer and provides an overview of the field as well as specific examples of how these diverse molecules regulate tumor behavior. © Springer Science+Business Media, LLC 2010. All rights reserved.