Cadherins are single-pass transmembrane proteins that, through their homophilic specificity, function in selective cell adhesion and sorting. They have a modular structure that includes an ectodomain composed of tandem 'cadherin domains,' which have a beta-sandwich topology similar to that of immunoglobulin domains. Some early experiments suggest that, for the 'classical' cadherins, the adhesive specificity is encoded in the membrane-distal amino-terminal cadherin domain. Here, we review these data, and present new data that supports this idea.