Ubiquitylation is a post-translational modification process in which a ubiquitin protein is bonded to a substrate protein. Ubiquitylation regulates a number of functions in the cell, including DNA repair, cell cycle control, endocytosis and cell signalling. This exciting field continues to grow, as potential small-molecule inhibitors emerge and new enzymes that regulate ubiquitin modifications are discovered. In this issue, we present a collection of three articles that focus on the topic of ubiquitylation from different angles. In our Cell Science to Watch interview (p. 1981), we talk with Mads Gyrd-Hansen, an associate professor at the Ludwig Institute for Cancer Research at the University of Oxford. Mads’ group is studying how ubiquitin modifications relay information from a receptor to the nucleus of the cell to drive transcriptional responses. Mads embarked on his study of ubiquitylation just as ubiquitin was emerging as a signalling molecule. He tells us about that exciting time, and discusses why ubiquitin is such a powerful signalling cue. There is mounting evidence that ubiquitylation plays a key role in the host infection strategy used by pathogenic bacteria. In our first Commentary on p. 1985, Yi-Han Lin and Matthias P. Machner discuss how bacterial effector proteins are ‘master manipulators’ of the host ubiquitin system, with a particular focus on how bacterial pathogens manipulate, block or even benefit from the host ubiquitin machinery. The process of ubiquitylation can be reversed by the action of deubiquitylating enzymes (DUBs), which are key regulators of many intracellular processes. There are many recent reports that address the mechanisms of action and biological roles of DUBs, but obtaining a complete picture is still far off. In our second Commentary on p. 1997, Pawel Leznicki and Yogesh Kulathu examine the different layers of regulation and diversification of DUB activity, and set directions for future research.