Multiple post-translational regulation systems regulate cell biology. Two key mechanisms that coordinate the myriad processes of cell replication are phosphorylation and ubiquitin-mediated degradation of proteins. Regulatory modules have evolved to integrate these two control systems at key decision points in the cell division cycle. These modules enable information to be processed with high fidelity by filtering noise, improving specificity, generating feedback loops, and optimizing spatiotemporal coordination of cellular processes. This review provides examples of these modules and considers the advantages of this signaling nexus.