Ubiquitination is emerging as a common regulatory mechanism that controls a range of cellular processes in plants. Recent exciting discoveries from several laboratories suggest that ubiquitination may also play an important role in plant disease resistance. Several putative ubiquitin ligases have been identified as defence regulators. In addition, a combination of genetic screens and gene-silencing technologies has identified subunits and proposed regulators of SCF ubiquitin ligases as essential components of resistance (R)-gene-mediated resistance. Although no ubiquitin ligase targets that are associated with disease resistance have yet been identified in plants, there is evidence that this well-known protein-modification system may regulate plant defences against pathogens.