Abstract: The use of single-agent no longer meets the requirements of complex disease treatment in current clinical practice. The combination of multiple drugs can often enhance the efficacy or reduce the adverse reaction of drugs, thus reflecting the synergistic advantages of drug combination. Therefore, the investigation of drug synergy is meaningful for the new drug discovery as well as the optimization of clinical treatment programme. Compared with the traditional experimental methods, pharmacoinformatics is a promising way to identify the synergistic effect of drug combination because of its fast, lower-cost, and green characteristics. This article reviews the advances in the databases that include the information of drug and disease, computational models and applications of the synergistic effect of drug combination from the perspective of pharmacoinformatics approaches, so as to provide reference for the development of new analysis models for drug synergy.