Approximately 2.5% of human gene products contain one or more small domains that drive interactions between proteins and other cellular components in cell signaling processes. The many interactions driven by these relatively simple domains are thought to cooperate with one another to yield complex signaling networks that allow very fine control of cell function. In principle, if we can understand all domain-mediated interactions it should be possible to model these networks. Genome-wide analysis of signaling domain interactions represents a first step in this direction, and several advances of this sort in yeast have been reported over the past year. These reports suggest, for some domains at least, that the prospect of generating 'wiring diagrams' with this simple approach is feasible.