In addition to the well-known metabolic functions of NAD and NADP, it is rapidly emerging that these 2 pyridine nucleotides and their derivatives also play important roles in cell signaling. Surprisingly, a number of NAD(P) metabolizing enzymes and NAD(P) targets have been found on the outer surface of the plasma membrane and the presence of NAD has been confirmed in extracellular fluids. These findings have opened the door to a new field of research aimed at elucidating the contribution of extracellular pyridine nucleotides in physiological signaling pathways and pathological conditions.