NAD + and its metabolites serve important functions in intracellular signalling. NAD + -mediated regulatory processes also take place on the cell surface, particularly of immune cells. In this issue of the Biochemical Journal , Gerth et al. have demonstrated a new mechanism of Ca 2+ uptake into monocytes which is triggered by NAD + or its degradation product, ADP-ribose. These observations point to a hitherto unknown Ca 2+ -influx mechanism and underscore the potential significance of NAD + and ADP-ribose as signalling molecules on the extracellular side of the plasma membrane.