Tissue morphogenesis during development is dependent on activities of the cadherin family of cell-cell adhesion proteins that includes classical cadherins, protocadherins, and atypical cadherins (Fat, Dachsous, and Flamingo). The extracellular domain of cadherins contains characteristic repeats that regulate homophilic and heterophilic interactions during adhesion and cell sorting. Although cadherins may have originated to facilitate mechanical cell-cell adhesion, they have evolved to function in many other aspects of morphogenesis. These additional roles rely on cadherin interactions with a wide range of binding partners that modify their expression and adhesion activity by local regulation of the actin cytoskeleton and diverse signaling pathways. Here we examine how different members of the cadherin family act in different developmental contexts, and discuss the mechanisms involved.Cadherins were originally identified as cell surface glycoproteins responsible for Ca 2+ -dependent homophilic cell-cell adhesion during morula compaction in the preimplantation mouse embryo and during chick development (Yoshida and Takeichi 1982;Gallin et al. 1983;Peyrieras et al. 1983). Subsequently, >100 family members have been identified with diverse protein structures, but all with characteristic extracellular cadherin repeats (ECs) (Nollet et al. 2000). Cadherins are important in both simple and complex organisms. In addition to vertebrates, insects, and nematodes, members of the cadherin family are found in unicellular choanoflagellates (King et al. 2003), the diploblast Hydra (Hobmayer et al. 2000), and the sponge Oscarella carmela (Nichols et al. 2006).In the three decades since their discovery, it has become clear that the role of cadherins is not limited to mechanical adhesion between cells. Rather, cadherin function extends to multiple aspects of tissue morphogenesis, including cell recognition and sorting, boundary formation and maintenance, coordinated cell movements, and the induction and maintenance of structural and functional cell and tissue polarity. Cadherins have been implicated in the formation and maintenance of diverse tissues and organs ranging from polarization of simple epithelia, to mechanically linking hair cells in the cochlea, to providing an adhesion code for neural circuit formation during wiring of the brain (Yagi and Takeichi 2000;Gumbiner 2005). Given the breadth of their functions, it is not surprising that defective cadherin expression has also been linked directly to a wide variety of diseases including the archetypal disruption of normal tissue architecture, metastatic cancer .The large size of the cadherin family and the structural diversity of its members may have evolved to enable the many types of cell interactions required for tissue morphogenesis in complex organisms. The number of cadherins as well as distinct features of their gene structure permit precise temporal and spatial transcriptional regulation of cadherin subtypes, and variations in protein structure, particularly the cytopl...