Defining what a healthy microbiome is proves to be a very difficult task, simply because there are many things we don’t know yet. Even in healthy people, there are immense variations in the composition of the microbiome, making the concept of a healthy microbiome very challenging. However, there are certain things that we do know. For example, that there is a strong link between a high microbial diversity in the gut and overall health, while a relative lack of diversity is common in many diseases. If one thing is for certain, it is that the microbiome is subject to constant change. Although a person’s microbiome is originally determined by one’s DNA and the transmission of microbes from mother to infant in the birth canal, it changes with age, the effects of diet, medications, ethnicity, geography, and lifestyle. One important milestone of the Human Microbiome Action will be to establish a definition for the healthy microbiome.