Inhibition of ADP‐ribosyltransferases with diphtheria toxin homology (ARTD), widely known as the poly(ADP‐ribose) polymerase (PARP) family, is a strategy under development for treatment of various conditions, including cancers and ischemia. Here, we give a brief summary of ARTD enzyme functions and the implications for their potential as therapeutic targets. We present an overview of the PARP inhibitors that have been used in clinical trials. Finally, we summarize recent insights from structural biology, and discuss the molecular aspects of PARP inhibitors in terms of broad‐range versus selective inhibition of ARTD family enzymes.