The L1 family of cell adhesion molecules (L1CAMs) in vertebrates has long been studied for its roles in nervous system development and function. Members of this family have been associated with distinct neurological disorders that include CRASH, autism, 3p syndrome, and schizophrenia. The conservation of L1CAMs in Drosophila and Caenorhabditis elegans allows the opportunity to take advantage of these simple model organisms and their accessible genetic manipulations to dissect L1CAM functions and mechanisms of action. This review summarizes the discoveries of L1CAMs made in C. elegans, showcasing this simple model organism as a powerful system to uncover L1CAM mechanisms and roles in healthy and diseased states. Developmental Dynamics 239:1490–1501, 2010. © 2010 Wiley-Liss, Inc.