The CXC chemokine family are unique cytokines known for their ability to have dual functions in the regulation of angiogenesis related to the following: (1) the presence or absence of the structural/functional motif (Glutamic acid-Leucine-Arginine; ‘ELR’ motif) that immediately precedes the first cysteine amino acid residue in the primary structure of these chemokines; (2) interferon-inducible gene expression; and (3) specific receptor interaction on endothelial cells. In this review we will appraise the biology of these angiogenic and angiostatic CXC chemokines, and discuss their disparate angiogenic activity in the context of the pathogenesis of cancer.