Chemokines are a key component of cancer-related inflammation. Chemokines and chemokine receptors are downstream of genetic events that cause neoplastic transformation and are components of chronic inflammatory conditions, which predispose to cancer. Components of the chemokine system affect in a cell autonomous or non-autonomous way multiple pathways of tumor progression, including: leukocyte recruitment and function; cellular senescence; tumor cell proliferation and survival; invasion and metastasis. Available information in preclinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies.