Traditional Chinese Medicine (TCM), with a clinical history of thousands of years, plays an important role in maintaining the health of Chinese peoples and is gaining more and more applications all over the world. The principle of principal, complement, assistant and guide is an important guideline to the prescription and formulation of TCM. The principal is so-called the main drug in the prescription or formulation which is used for the main symptoms and solves the major problems associated with the disease. The assistant is the supplementary drug in the prescription or formulation, which is located in a secondary position and has two roles. Firstly, it is usually used for the minor symptoms and complications. Secondly, it improves the efficacy of main drugs. The complement is also a significant part which usually has three functions. Firstly, it is used to improve the efficacy of main drugs or direct treat minor symptoms. Secondly, it reduces the side effects of the principal and assistant. Lastly, it also reduces the drug resistance developed during the long term use. The guide has two functions in the prescription or formulation. It guides the drug to the focus of the disease and reduces the side effects resulting from the principal and assistant.

This principle coincides with the theory of combination therapy which is advocated by the modern western medicine. Modern medicine emphasizes the combinational formulation of drugs based on the individual situation of the patients to improve the efficacy and reduce the side effects of drugs. Combination therapy may influence the related enzymes, transporters, etc., which are associated with drug absorption, distribution, metabolism and excretion, in order to change the pharmacokinetic properties (bioavailability, distribution etc.), strength the efficacy (synergy of drugs, antagonism, side effects, etc.), and influence the safety of drugs.

Although there are many resemblances between them, they have many differences. Firstly, they have different theoretical basis. The theoretical basis of the principle of principal, assistant, complement and guide is the dialectical treatment. It is based on the patient's individual constitution and symptoms to give a combination of different drugs to achieve symptomatic and individualized treatment. We do not know the specific components of most of the Chinese medicines and decide whether they could be used together only based on their so-called flavor and meridian tropism. The combination therapy is based on chemistry and pharmacology, thus; we need to know the specific ingredients of each drug and whether they interact with each other in vivo. And we also should know what the reaction products are and whether these products could interact again. Secondly, the prescriptions of TCM are composed of dominant and auxiliary drugs while there is no clear distinction between the members in combination therapy.

The principle of principal, assistant, complement, and guide in TCM is so popular that it is hardly to find a prescription or formulation without its application. However, this principle is also facing many challenges. Modern pharmacy emphasizes clear components, whereas the components of TCM are not yet all clear due to various reasons. This makes many people doubt the efficacy and safety of TCM. The principle is derived from the medication experience and has been proved in the long history. Although we are confident in its safety, modern theory and techniques should be used to evidence its validity and rationality. The good news is that a lot of researchers are now working to investigate the composition and mechanism of TCM and have achieved good results. We believe that TCM will provide better services for human health with the joint efforts of medical workers.