Growth factors, hormones, cytokines and second messengers – the list of components that can activate intracellular signals through specific cell-surface receptors and, thereby, change cellular behaviour seems endless. However, cells not only respond to chemical signals. They are also able to sense changes in their extracellular environment and to react to mechanical stress. The process by which such mechanical signals are translated into biochemical signals – referred to as ‘mechanotransduction’ – is the focus of the six Commentaries in this issue's Minifocus. On page 3015, Brendon Baker and Chris Chen discuss how microenvironmental cues differ in two and three dimensions. Mike Sheetz and co-authors (p. 3025) summarise force transmission through integrins and the adaptor proteins associated with them, whereas Ulrich Schwarz and Margaret Gardel (p. 3051) explore the roles of focal adhesion and actin dynamics in mechanotransduction. On page 3039, Huimin Zhang and Michel Labouesse explain how forces are generated in a different organisms and the processes that translate them into biochemical signals. Don Ingber and colleagues (p. 3061) explore how mechanical cues influence transcriptional processes in development and homeostasis. On page 3075, Sergei Sukharev and Frederick Sachs provide an overview of how mechanosensitive ion channels sense and transmit mechanical stresses.