Abstract: Traditional Chinese medicines (TCMs) have been used to prevent and treat various diseases for thousands of years. Promoting efficacy and reducing toxicity by the compatibility theory of TCMs has attracted increasing attention, especially for the toxicity of herbs. Studies have pointed out the interactions between the active compounds of herbs and transporters in the detoxification process of toxic compounds. Here, we summarize data on five toxic herbs commonly used in TCMs and their related efflux transporters to reduce toxicity to offer a scientific rationale for the compatibility principle of TCMs and provide guidance for the rational clinical use of TCMs.