The amino acid sequences of a large number of the cell surface proteins known to mediate cell-cell interactions in the nervous system have recently been reported. Many of these proteins are members of the immunoglobulin gene superfamily and have remarkably similar structures and amino acid sequences in their extracellular segments. We have termed this family of immunoglobulin-related cell adhesion molecules the Ig-CAMs. In this article, we review the structural features of the Ig-CAMs, discuss how these features may relate to the role of these proteins in mediating cell adhesion and cell signaling events, and finally consider the evolutionary origins of this family of proteins.