Gene transcription can be activated or repressed. Such seemingly simple decisions reflect the coordinated actions of a wide array of proteins. Activators and co-activators work together to stimulate the assembly and activity of the machinery that transcribes the gene, whereas repressors and co-repressors work to achieve the opposite goal. Recent studies show that many proteins often engage in regulatory activities and interactions that cross the activation-repression divide. This article discusses selected examples to illustrate the dynamic nature of the transcriptional regulation process and highlights the important roles of not only the individual proteins but also their communication system.