Unlike poly(ADP-ribose) polymerase-1 (PARP-1), poly(ADP-ribose) glycohydrolase (PARG) has long been a difficult protein to study. However, the complete absence of PARG activity was recently characterized in mice via disruption of the murine PARG gene. As expected, PARG is critical for the maintenance of steady-state poly(ADP-ribose) levels. But surprisingly, the disruption of PARG led to embryonic lethality and increased susceptibility to mild cell stress. Therefore, the protective role of PARG and its involvement in development indicate that these roads to viability go through PARG.