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 Ca2+ uptake into monocytes which is triggered by NAD+ or its degradation product, ADP-ribose. These observations point to a hitherto unknown Ca2+-influx mechanism and underscore the potential significance of NAD+ and ADP-ribose as signalling molecules on the extracellular side of the plasma membrane.