Chemokines regulate leukocyte migration during physiological and pathological conditions. It is currently accepted that these chemotactic cytokines are also important in the development and progression of cancer. CXCL4 and its non-allelic variant CXCL4L1 are two platelet-associated chemokines that have been attributed anti-tumoral activity as a result of their angiostatic potential and the chemotactic activity for anti-tumoral leukocytes. Here we review the role of CXCL4 and CXCL4L1 in cancer, the use of both chemokines as cancer biomarkers and discuss some possible therapeutic opportunities.