Welcome to this Fourth Special Issue of Molecular Biology of the Cell on Forces on and within Cells. As with our other Special Issues, the journal’s goal here is to focus attention on a major new direction in cell biology. In this case, it is the field of mechanobiology, which endeavours, broadly, to understand how mechanical forces are harnessed to drive cellular function and how force can also be a mode of biological information that regulates cell behavior. The collection of papers that we have in this issue reflects many current efforts to address these questions. While each of these papers is a distinct creative effort of its authors, I would like to draw your attention to a number of themes that emerge across these diverse studies.