With the recent addition of anti-angiogenic agents to cancer treatment, the angiogenesis regulators in platelets are gaining importance. Platelet factor 4 (PF-4/CXCL4) and Connective tissue activating peptide III (CTAP-III) are two platelet-associated chemokines that modulate tumor angiogenesis, inflammation within the tumor microenvironment, and in turn tumor growth. Here, we review the role of PF-4 and CTAP-III in the regulation of tumor angiogenesis; the results of clinical trial using recombinant PF-4 (rPF-4); and the use of PF-4 and CTAP-III as cancer biomarkers.