Eph receptor protein-tyrosine kinases are among the oldest known animal receptors and have greatly expanded in number during vertebrate evolution. Their complex transduction mechanisms are capable of bidirectional and bimodal (multi-response) signaling. Eph receptors are expressed in almost every cell type in the human body, yet their roles in development, physiology, and disease are incompletely understood. Studies in C. elegans have helped identify biological functions of these receptors, as well as transduction mechanisms. Here we review advances in our understanding of Eph receptor signaling made using the C. elegans model system.