Inhibiting deubiquitinase (DUB) function is a promising strategy for the treatment of cancers and other human diseases. Of the hundreds of human DUBs, USP11 has emerged as an ideal therapeutic target, as it regulates DNA double-strand break repair by homologous recombination (HR) and other functions central to eukaryotic cell survival. A new study by Spiliotopoulos et al. cleverly uses next-generation phage display (NGPD) to identify peptide ligands that bind USP11 in a unique pocket that impacts HR. The study provides an important step toward novel DUB inhibitors that may reduce the resistance of some cancers to current treatment options.