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ADP‐ribosylation is the addition of one or more (up to some hundreds) ADP‐ribose moieties to acceptor proteins. There are two major families of enzymes that catalyse this reaction: extracellular ADP‐ribosyl‐transferases (ARTs), which are bound to the cell membrane by a glycosylphosphatidylinositol anchor or are secreted, and poly(ADP‐ribose)‐polymerases (PARPs), which are present in the cell nucleus and/or cytoplasm. Recent findings revealed a wide immunological role for ADP‐ribosylating enzymes. ARTs, by sensing extracellular NAD concentration, can act as danger detectors. PARP‐1, the prototypical representative of the PARP family, known to protect cells from genomic instability, is involved in the development of inflammatory responses and several forms of cell death. PARP‐1 also plays a role in adaptive immunity by modulating the ability of dendritic cells to stimulate T cells or by directly affecting …