Mono-ADP-ribosylation, like phosphorylation, is an enzyme-catalyzed, reversible post-translational modification that modulates protein function. It was originally discovered as the pathogenic principle of diphtheria-, cholera-, and other potent bacterial toxins. By analogy, corresponding enyzmes were postulated to exist in animal tissues, and mounting biochemical evidence indicates that such enzymes, indeed, play important regulatory roles in cellular functions. The molecular cloning of the first mammalian mono(ADP-ribosyl)transferase from rabbit skeletal muscle, the finding of its homology to a well-studied T-cell marker, RT6, and the molecular cloning of additional gene family members from mammals and birds is providing fresh impetus to research in this field. Intriguingly, these vertebrate enzymes are predicted to be secretory or membrane proteins. They are expressed in lymphatic tissues, muscle, testis, bone marrow, and erythroblasts. Here we review the relationship between this novel family of eucaryotic mono(ADP-ribosyl)transferases (mADPRTs), ADP-ribosylating bacterial toxins, the poly(ADP-ribose)polymerase (PARP), the ADP-ribosyl cyclases, and the ADP-ribosylprotein hydrolase (ARH) in terms of their structure, enzymatic properties and possible biological functions.