MAP-kinase signaling pathways are activated by multiple extracellular stimuli. The specificity of activation and function of MAP-kinase signaling modules is determined, in part, by scaffold proteins that create multienzyme complexes. In Saccharomyces cerevisiae, two MAP-kinase-scaffold proteins have been identified. Recent studies of mammalian cells have also led to the identification of putative scaffold proteins. These scaffold proteins appear to facilitate MAP-kinase activation, in response to specific physiological stimuli, and to insulate the bound MAP-kinase module against activation by irrelevant stimuli. Scaffold proteins are therefore critical components of MAP-kinase modules and ensure signaling specificity.