Inspired by viruses and parasites that protect themselves from host immune system with the help of neutralizing substances that block the action of chemokines, an emerging class of new compounds with anti-inflammatory and anticancer properties can be developed. These small chemicals interact with the chemokine to prevent its actions on the subset of its natural target chemokine receptors. A proof of concept, given by a small molecule that neutralize CXCL12, and act in vivo as anti-inflammatory in a mouse model of airway hypereosinophilia will be illustrated. Strategies to identify and characterize such ‘neutraligands’ are presented, as well as their potential interest in the therapeutic armamentarium targeting chemokine signaling is discussed.