Cell-surface/extracellular-matrix heparan-sulphate glycosaminoglycans (HSGAGs) are complex polysaccharides that are ubiquitous in nature, and that regulate several aspects of cancer biology, including tumorigenesis, tumour progression and metastasis. Recently gained insights into the structure of HSGAGs have extended our understanding of their role in the oncogenic process. At present, clinical trials are examining the anticancer properties of exogenous highly sulphated HSGAGs, including heparin and low-molecular-weight heparins, in addition to small oligosaccharide heparin mimetics. Combined with our more intricate understanding of HSGAG structure, this emerging structure–activity approach opens exciting avenues for the generation of polysaccharide-based anticancer therapeutics.