Cadherins are Ca(2+)-dependent cell adhesion molecules found in several kinds of cell-cell contact, including adherens junctions and desmosomes. In the presence of Ca(2+), cells expressing the same type of cadherin form stable contacts with one another, a phenomenon designated homophilic, or homotypic, adhesion. Most cadherins are single-pass transmembrane proteins whose extracellular regions mediate specific cell-cell interactions. The intracellular faces of these contacts are associated with the actin cytoskeleton in adherens junctions or the intermediate-filament system in desmosomes. The close coordination of the transmembrane adhesion molecules with the cytoskeleton is believed to be essential in coordinating morphogenetic movements of tissues during development and in conferring the appropriate mechanical properties to cell-cell contacts. Structural, biochemical, and biophysical analysis of the molecules that comprise these contacts has provided unique mechanistic insights into the specificity of homophilic adhesion, the functional connection to the underlying cytoskeleton, and the dynamics of junction formation.