Promoting effects of Cs, Re oxospecies, and Cl for silver catalysts of ethylene epoxidation are studied computationally using the DFT approach. The promoters are shown to enhance the extent of activation of initial substances, reaction intermediates, and products, while different combinations of promoters are favorable for different stages of the process. The synergistic effect of Cs, Re, and Cl is connected with the adjustment of the substrate location with respect to silver, thus, setting the favorable conditions for rapid transformation of ethylene into ethylene oxide. Re and Cl complement each other to balance and mitigate the effect of the Agbound Cs to alter the distribution of electronic density, tuning the electronic states of surface oxygen species by making it more electrophilic, and providing the substrate binding strength that ensures "optimal" substrate residence time and improves the catalyst performance in ethylene epoxidation.