It has been 10 years since the role of a chemokine receptor, CXCR4, in breast cancer metastasis was first documented. Since then, the field of chemokines and cancer has grown significantly, so it is timely to review the progress, analyse the studies to date and identify future challenges facing this field. Metastasis is the major factor that limits survival in most patients with cancer. Therefore, understanding the molecular mechanisms that control the metastatic behaviour of tumour cells is pivotal for treating cancer successfully. Substantial experimental and clinical evidence supports the conclusion that molecular mechanisms control organ-specific metastasis. One of the most important mechanisms operating in metastasis involves homeostatic chemokines and their receptors. Here, we review this field and propose a model of 'cellular highways' to explain the effects of homeostatic chemokines on cancer cells and how they influence metastasis.