Tumorigenesis may be affected by various cellular components in the tumor cells and/or by tumor microenvironmental factors. Cytokines, including chemokines (chemotactic cytokines) are polypeptides or small soluble proteins generated by leukocytes and non-leukocytes, including cancer cells and stromal cells, for example, fibroblasts, mesenchymal stem cells (MSCs) and epithelial cells. Cytokines exert their functions on the cells that secrete them, on nearby cells, or on distant cells. Chemokines have expanded beyond their initial roles in impinging on every aspect of the immune system and leukocyte biology. They display multifunctional effects for regulating angiogenesis, tumor cell proliferation and apoptosis, mediating tumor cell metastasis in an organ-specific manner. This review will focus on the structural and functional aspects of chemokines as well as the roles that cytokines and their receptors play in angiogenesis, tumor invasion and metastasis, and discuss their potential value as important therapeutic targets for intervention in cancer.