Intrinsically disordered proteins (IDPs) mediate critical regulatory functions in the cell, including regulation of transcription, translation, the cell cycle, and numerous signal transduction events. In keeping with their regulatory function, the cellular abundance of intrinsically disordered proteins is tightly controlled. Many viruses hijack their host cells by making extremely effective use of intrinsic disorder to mimic key cellular regulatory proteins that are themselves intrinsically disordered. The lack of stable globular structure can confer numerous functional advantages, including, paradoxically, both binding promiscuity and high specificity in target interactions. IDPs frequently function in dynamic regulatory networks, where their propensity for posttranslational modifications, their rapid binding and dissociation kinetics, and their ability to interact with multiple target proteins makes them well adapted for precise transduction of cellular signals. The role of IDPs in dynamic cellular signaling will be illustrated by reference to pathways regulated by the general transcriptional coactivators CBP and p300, the tumor suppressor p53, and the adenovirus E1A oncoprotein. CBP and p300 are central nodes in eukaryotic transcriptional regulatory networks and transcription factors must compete for binding to the limiting concentrations of CBP/p300 present in the cell. Many intrinsically disordered proteins contain multipartite interaction motifs that perform an essential function in the integration of complex signaling networks. The role of multipartite binding motifs and post translational modifications in regulation of p53-mediated signaling pathways will be discussed.