Abstract: Combining herbs is a characteristic advantage of traditional Chinese medicines (TCMs)， done for many thousands of years， and is an important way to reduce the side effects or toxicity caused by TCMs. Here， we introduced the different approaches to investigate the compatibility for the reducing toxicity， using a case of our studies on the compatibility between bezoar and toad venom. These approaches includes mining Chinese medicine theory and clinic data， toxicological evaluation in vivo and in vitro， analysis of chemical constituents， and pharmacokinetic interaction of components， and use of molecular biology or -omics techniques. They could be crucial ways in the development of modern TCMs with better safety that will reinforce advancement to this field.