Proteoglycans (PGs) and glycosaminoglycans (GAGs) are essential molecules to guarantee cell proliferation, interaction with extracellular matrix (ECM) compounds, and several other processes crucial to homeostasis maintenance. However, when GAGs and PGs synthesis or shedding is uncontrolled, they can favor or block several cancer hallmarks, depending on GAGs or PGs type, structural modifications, amounts, and location. In this chapter, we will approach the structure, biosynthesis, and general and specific functions of heparan sulfate (HS), heparin (Hep), chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS), and their respective PGs, as wells as the non-sulfated GAG, the hyaluronic acid (HA), with a focus in their roles in cancer. The PGs section is organized according to the GAGs chains in the PG structure: HS PGs, HS/CS PGs, Hep/CS PGs, CS PGs, CS and/or DS/HS PGs, DS PGs, and KS PGs. We will also approach the enzymes responsible for modifications in GAGs and PGs structures in cancer, such as heparanase, sulfatases, and sheddases. The data summarized in this chapter will contribute to the reader’s comprehension of this complex field, helping to fill the gaps in the GAGs/PGs knowledge of cancer and improving the development of anticancer targeted therapies.