Most chronic diseases impairing current human public health involve not only the human genome but also gene鈥揺nvironment interactions, and in the latter case the gut microbiome is an important factor. This makes the classical single drug鈥搑eceptor target drug discovery paradigm much less applicable. There is widespread and increasing international interest in understanding the properties of traditional Chinese medicines (TCMs) for their potential utilization as a source of new drugs for Western markets as emerging evidence indicates that most TCM drugs are actually targeting both the host and its symbiotic microbes. In this review, we explore the challenges of and opportunities for harmonizing Eastern鈥揥estern drug discovery paradigms by focusing on emergent functions at the whole body level of humans as superorganisms. This could lead to new drug candidate compounds for chronic diseases targeting receptors outside the currently accepted 鈥渄ruggable genome鈥?and shed light on current high interest issues in Western medicine such as drug鈥揹rug and drug鈥揹iet鈥揼ut microbial interactions that will be crucial in the development and delivery of future therapeutic regimes optimized for the individual patient.