Germ-free, or GF, animals are laboratory animals that completely lack microbes, making them useful tools for microbiome research. Researchers create GF animals in laboratories by delivering the newborn animals in a way that protects them from microbes, which are microscopic organisms such as bacteria and viruses. They then house the GF animals in sterile conditions to ensure that the animals stay germ free. The creation of GF animals began in the late nineteenth century. Prior to that, scientists had no way to study the effects of the microbiome on overall health. The creation of GF animals allowed researchers to examine the microbiome under controlled conditions. They could colonize the animal with specific microbes and study their effects on the animal’s health without the confounding presence of other microbes. Researchers have used GF animals as a living model to study the microbiome, which has provided evidence for a relationship between the microbiome and health, including a role for the microbiome in shaping the development of multiple body systems.