In 1901, the first Nobel Prize in Physiology or Medicine was awarded to Emil von Behring for his ground-breaking discovery of serum therapy: serum from horses vaccinated with toxin-containing culture medium of Corynebacterium diphtheria contained life-saving "Antitoxins". The molecular nature of the ADP-ribosylating toxin and the neutralizing antibodies were unraveled only 50 years later. Today, von Behring's antibody therapy is being refined by a new generation of recombinant antibodies and antibody-fragments. Nanobodies, single domain antibodies derived from the peculiar heavy chain antibodies of llamas and other camelids, are emerging as a promising new class of highly specific enzyme inhibitors. In this review we illustrate the potential of Nanobodies as tools to block extracellular and intracellular ADP-ribosyltransferases using the toxin-related membrane bound mammalian ecto-enzyme ARTC2 and the actin-ADP-ribosylating SpvB toxin of Salmonella entericae as examples. This article is protected by copyright. All rights reserved.