Cell–cell contacts are major determinants of tissue organization in both health and disease. Adhesive interactions, especially those mediated by classical cadherin receptors, influence cell–cell recognition and tissue patterning during development. Conversely, cadherin dysfunction promotes tumor progression to invasion and metastasis. Over the past three decades, we have learnt a great deal about the molecular mechanisms responsible for cadherin-based cell–cell interactions. Yet our knowledge remains incomplete. The intersection between cell biology and mechanical forces has long been suspected to be an important missing factor in understanding cadherin biology. However, tangible evidence remained elusive until recently, when several reports began to elucidate the role of cadherins and the cytoskeleton in mechanotransduction. In this review, we examine these advances and discuss their implications.