Over the course of four billion years, humans have developed an intimate relationship with the more than 37 trillion microbes that inhabit our bodies. This relationship runs the gamut from symbiosis to pathogenesis. The number of microbial cells is roughly equivalent to that of mammalian cells in the body. However, due to substantial microbial diversity in host-associated communities, the genetic content of the microbiome is roughly 150 times greater than that of the human genome. Microbial genes encode for proteins capable of producing a wide variety of molecules essential for our health and survival. Many factors such as mode of birth, diet, chlorination of water, and medications significantly affect the richness and diversity of the microbiome. Advanced practice nurses have important roles to play as clinicians, scientists, educators, and patient advocates as our understanding of the microbiome's effects on health becomes better articulated. An understanding of how the microbiome can affect an individual's health or the efficacy of treatment will soon be essential in the clinical setting, and nurses should be encouraged to educate themselves on the relationship between our microbial partners, the environment, and human health.