Bias in chemokine receptor signalling

•Variations in chemokine expression control the function of immune cells. •Biased signalling has been reported for six different chemokine receptors. •Drugs can differently affect multiple chemokines that bind to a chemokine receptor. •Biased signalling by drugs could improve pharmacological profiles. Chemokine receptors are widely expressed on a variety of immune cells and play a crucial role in normal physiology as well as in inflammatory and infectious diseases. The existence of 23 chemokine receptors and 48 chemokine ligands guarantees a tight control and fine-tuning of the immune system. Here, we discuss the multiple regulatory mechanisms of chemokine signalling at a systemic, cellular, and molecular level. In particular, we focus on the impact of biased signalling at the receptor level; an emerging concept in molecular pharmacology. An improved understanding of these mechanisms may provide a framework for more effective drug discovery and development at a target class that is so relevant for immune function. Chemokine receptors are widely expressed on a variety of immune cells and play a crucial role in normal physiology as well as in inflammatory and infectious diseases. The existence of 23 chemokine receptors and 48 chemokine ligands guarantees a tight control and fine-tuning of the immune system. Here, we discuss the multiple regulatory mechanisms of chemokine signalling at a systemic, cellular, and molecular level. In particular, we focus on the impact of biased signalling at the receptor level; an emerging concept in molecular pharmacology. An improved understanding of these mechanisms may provide a framework for more effective drug discovery and development at a target class that is so relevant for immune function.