Casein lytic peptidase P (ClpP) is a serine peptidase that, when coupled to its cognate ATPase, facilitates the controlled degradation of both damaged and unwanted proteins in bacteria. In this issue of Chemistry & Biology, Leung et al. (2011) report a small molecule screen against ClpP, from which they identified four structurally distinct compounds that activate ClpP for unregulated proteolysis.