The article presents research highlights from the field of therapeutics based on the original research paper "An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer," by T.A. Soucy et al. that appeared in issue 458, 2009 of "Nature." Subjects discussed include how to target the ubiquitin-proteasome system (UPS), cullin-RING ligases (CRLs), xenografts, and DNA replication factor 1 (CDT1).