Heparin is frequently used in the treatment of cancer-associated thromboembolism. Accumulating clinical evidence indicates that cancer patients treated with unfractionated and low-molecular weight heparin (LMWH) survive longer than patients treated by other anticoagulants, especially patients in the early stage of the disease. Experimental analysis from a number of animal models constantly provides evidence for the ability of heparin to attenuate metastasis. The non-anticoagulant activity of heparin on metastasis includes the ability to inhibit cell-cell-interaction through blocking of P- and L-selectin, to inhibit extracellular matrix protease heparanase, and to inhibit angiogenesis. This chapter summarizes current experimental evidence on the biology of heparin during cancer progression, with the focus on potential mechanism of heparin antimetastatic activity.