The process of signal transduction is dependent on specific protein-protein interactions. In many cases, these interactions are mediated by modular protein domains that confer specific binding activity to the proteins in which they are found. Rapid progress has been made in the biochemical characterization of binding interactions, the identification of binding partners, and determination of the three-dimensional structures of binding modules and their ligands. The resulting information establishes the logical framework for our current understanding of the signal transduction machinery. In this chapter, a variety of protein interaction modules that participate in signaling are discussed, and issues relating to binding specificity and the significance of a particular interaction are considered.